Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment
Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to b...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Maldonado, Maria del Mar [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Anmerkung: |
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 |
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| Übergeordnetes Werk: |
Enthalten in: Cancer immunology immunotherapy - Berlin : Springer, 1976, 72(2023), 10 vom: 28. Juli, Seite 3349-3362 |
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| Übergeordnetes Werk: |
volume:72 ; year:2023 ; number:10 ; day:28 ; month:07 ; pages:3349-3362 |
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| DOI / URN: |
10.1007/s00262-023-03496-2 |
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| Katalog-ID: |
SPR05301779X |
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| 245 | 1 | 0 | |a Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment |
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| 520 | |a Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. | ||
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| 700 | 1 | |a Hamilton, Duane H. |0 (orcid)0000-0002-9730-8209 |4 aut | |
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10.1007/s00262-023-03496-2 doi (DE-627)SPR05301779X (SPR)s00262-023-03496-2-e DE-627 ger DE-627 rakwb eng Maldonado, Maria del Mar verfasserin (orcid)0000-0001-6847-2707 aut Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. CSF1 (dpeaa)DE-He213 CSF1R (dpeaa)DE-He213 Tumor-associated macrophages (dpeaa)DE-He213 Cancer vaccines (dpeaa)DE-He213 Epitope spreading (dpeaa)DE-He213 Schlom, Jeffrey (orcid)0000-0001-7932-4072 aut Hamilton, Duane H. (orcid)0000-0002-9730-8209 aut Enthalten in Cancer immunology immunotherapy Berlin : Springer, 1976 72(2023), 10 vom: 28. Juli, Seite 3349-3362 (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 https://dx.doi.org/10.1007/s00262-023-03496-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 72 2023 10 28 07 3349-3362 |
| spelling |
10.1007/s00262-023-03496-2 doi (DE-627)SPR05301779X (SPR)s00262-023-03496-2-e DE-627 ger DE-627 rakwb eng Maldonado, Maria del Mar verfasserin (orcid)0000-0001-6847-2707 aut Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. CSF1 (dpeaa)DE-He213 CSF1R (dpeaa)DE-He213 Tumor-associated macrophages (dpeaa)DE-He213 Cancer vaccines (dpeaa)DE-He213 Epitope spreading (dpeaa)DE-He213 Schlom, Jeffrey (orcid)0000-0001-7932-4072 aut Hamilton, Duane H. (orcid)0000-0002-9730-8209 aut Enthalten in Cancer immunology immunotherapy Berlin : Springer, 1976 72(2023), 10 vom: 28. Juli, Seite 3349-3362 (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 https://dx.doi.org/10.1007/s00262-023-03496-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 72 2023 10 28 07 3349-3362 |
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10.1007/s00262-023-03496-2 doi (DE-627)SPR05301779X (SPR)s00262-023-03496-2-e DE-627 ger DE-627 rakwb eng Maldonado, Maria del Mar verfasserin (orcid)0000-0001-6847-2707 aut Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. CSF1 (dpeaa)DE-He213 CSF1R (dpeaa)DE-He213 Tumor-associated macrophages (dpeaa)DE-He213 Cancer vaccines (dpeaa)DE-He213 Epitope spreading (dpeaa)DE-He213 Schlom, Jeffrey (orcid)0000-0001-7932-4072 aut Hamilton, Duane H. (orcid)0000-0002-9730-8209 aut Enthalten in Cancer immunology immunotherapy Berlin : Springer, 1976 72(2023), 10 vom: 28. Juli, Seite 3349-3362 (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 https://dx.doi.org/10.1007/s00262-023-03496-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 72 2023 10 28 07 3349-3362 |
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10.1007/s00262-023-03496-2 doi (DE-627)SPR05301779X (SPR)s00262-023-03496-2-e DE-627 ger DE-627 rakwb eng Maldonado, Maria del Mar verfasserin (orcid)0000-0001-6847-2707 aut Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. CSF1 (dpeaa)DE-He213 CSF1R (dpeaa)DE-He213 Tumor-associated macrophages (dpeaa)DE-He213 Cancer vaccines (dpeaa)DE-He213 Epitope spreading (dpeaa)DE-He213 Schlom, Jeffrey (orcid)0000-0001-7932-4072 aut Hamilton, Duane H. (orcid)0000-0002-9730-8209 aut Enthalten in Cancer immunology immunotherapy Berlin : Springer, 1976 72(2023), 10 vom: 28. Juli, Seite 3349-3362 (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 https://dx.doi.org/10.1007/s00262-023-03496-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 72 2023 10 28 07 3349-3362 |
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10.1007/s00262-023-03496-2 doi (DE-627)SPR05301779X (SPR)s00262-023-03496-2-e DE-627 ger DE-627 rakwb eng Maldonado, Maria del Mar verfasserin (orcid)0000-0001-6847-2707 aut Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. CSF1 (dpeaa)DE-He213 CSF1R (dpeaa)DE-He213 Tumor-associated macrophages (dpeaa)DE-He213 Cancer vaccines (dpeaa)DE-He213 Epitope spreading (dpeaa)DE-He213 Schlom, Jeffrey (orcid)0000-0001-7932-4072 aut Hamilton, Duane H. (orcid)0000-0002-9730-8209 aut Enthalten in Cancer immunology immunotherapy Berlin : Springer, 1976 72(2023), 10 vom: 28. Juli, Seite 3349-3362 (DE-627)253390443 (DE-600)1458489-X 1432-0851 nnns volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 https://dx.doi.org/10.1007/s00262-023-03496-2 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4277 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 72 2023 10 28 07 3349-3362 |
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Enthalten in Cancer immunology immunotherapy 72(2023), 10 vom: 28. Juli, Seite 3349-3362 volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 |
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Enthalten in Cancer immunology immunotherapy 72(2023), 10 vom: 28. Juli, Seite 3349-3362 volume:72 year:2023 number:10 day:28 month:07 pages:3349-3362 |
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CSF1 CSF1R Tumor-associated macrophages Cancer vaccines Epitope spreading |
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Cancer immunology immunotherapy |
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Maldonado, Maria del Mar @@aut@@ Schlom, Jeffrey @@aut@@ Hamilton, Duane H. @@aut@@ |
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In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. 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Maldonado, Maria del Mar |
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Maldonado, Maria del Mar misc CSF1 misc CSF1R misc Tumor-associated macrophages misc Cancer vaccines misc Epitope spreading Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment |
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Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment CSF1 (dpeaa)DE-He213 CSF1R (dpeaa)DE-He213 Tumor-associated macrophages (dpeaa)DE-He213 Cancer vaccines (dpeaa)DE-He213 Epitope spreading (dpeaa)DE-He213 |
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misc CSF1 misc CSF1R misc Tumor-associated macrophages misc Cancer vaccines misc Epitope spreading |
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Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment |
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Maldonado, Maria del Mar |
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Cancer immunology immunotherapy |
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blockade of tumor-derived colony-stimulating factor 1 (csf1) promotes an immune-permissive tumor microenvironment |
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Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment |
| abstract |
Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 |
| abstractGer |
Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 |
| abstract_unstemmed |
Abstract The macrophage colony-stimulating factor 1 (CSF1) is a chemokine essential for the survival, proliferation, and differentiation of mononuclear phagocytes from hemopoietic stem cells. In addition to its essential physiological role in normal tissues, the CSF1/CSF1 receptor axis is known to be overexpressed in many tumor types and associated with poor prognosis. High levels of CSF1 within the tumor microenvironment have been shown to recruit and reeducate macrophages to produce factors that promote tumor invasiveness and accelerate metastasis. In this study, we demonstrate, for the first time, that treating established syngeneic murine colon and breast carcinoma tumors with a CSF1R-blocking antibody also promotes the expansion of neoepitope-specific T cells. To assess the role of tumor-derived CSF1 in these model systems, we generated and characterized CSF1 CRISPR-Cas9 knockouts. Eliminating tumor-derived CSF1 results in decreased tumor growth and enhanced immunity against tumor-associated neoepitopes, potentially promoting an immune permissive tumor microenvironment in tumor-bearing mice. The combination of neoepitope vaccine with anti-PDL1 in the MC38 CSF1−/− tumor model significantly decreased tumor growth in vivo. Moreover, anti-CSF1R therapy combined with the adeno-TWIST1 vaccine resulted in tumor control, decreased metastasis, and a synergistic increase in CD8 T cell infiltration in 4T1 mammary tumors. Analysis of the tumor microenvironment demonstrated greater CD8 T cell infiltration and a reduction in tumor-associated macrophages following CSF1R inhibition in both tumor models. Our findings thus add to the therapeutic potential of CSF1 targeting agents by employing combinations with vaccines to modulate anti-neoepitope responses in the tumor microenvironment. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 |
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| title_short |
Blockade of tumor-derived colony-stimulating factor 1 (CSF1) promotes an immune-permissive tumor microenvironment |
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https://dx.doi.org/10.1007/s00262-023-03496-2 |
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Schlom, Jeffrey Hamilton, Duane H. |
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| doi_str |
10.1007/s00262-023-03496-2 |
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2024-07-03T16:28:15.601Z |
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| score |
7.4002256 |