Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma
Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-...
Ausführliche Beschreibung
Autor*in: |
Feng, Zipei [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2015 |
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Anmerkung: |
© Feng et al. 2015 |
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Übergeordnetes Werk: |
Enthalten in: Journal for ImmunoTherapy of Cancer - London : BioMed Central, 2013, 3(2015), 1 vom: 20. Okt. |
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Übergeordnetes Werk: |
volume:3 ; year:2015 ; number:1 ; day:20 ; month:10 |
Links: |
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DOI / URN: |
10.1186/s40425-015-0091-z |
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Katalog-ID: |
SPR03642868X |
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245 | 1 | 0 | |a Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma |
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520 | |a Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. | ||
650 | 4 | |a Tumor-infiltrating lymphocytes (TIL) |7 (dpeaa)DE-He213 | |
650 | 4 | |a multispectral imaging |7 (dpeaa)DE-He213 | |
650 | 4 | |a Adoptive T cell therapy (ACT) |7 (dpeaa)DE-He213 | |
650 | 4 | |a Immunotherapy |7 (dpeaa)DE-He213 | |
650 | 4 | |a Melanoma |7 (dpeaa)DE-He213 | |
650 | 4 | |a Immunoprofiling |7 (dpeaa)DE-He213 | |
650 | 4 | |a Immunoscore |7 (dpeaa)DE-He213 | |
650 | 4 | |a Immunotherapy biomarker |7 (dpeaa)DE-He213 | |
700 | 1 | |a Puri, Sachin |4 aut | |
700 | 1 | |a Moudgil, Tarsem |4 aut | |
700 | 1 | |a Wood, William |4 aut | |
700 | 1 | |a Hoyt, Clifford C. |4 aut | |
700 | 1 | |a Wang, Chichung |4 aut | |
700 | 1 | |a Urba, Walter J. |4 aut | |
700 | 1 | |a Curti, Brendan D. |4 aut | |
700 | 1 | |a Bifulco, Carlo B. |4 aut | |
700 | 1 | |a Fox, Bernard A. |4 aut | |
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10.1186/s40425-015-0091-z doi (DE-627)SPR03642868X (SPR)s40425-015-0091-z-e DE-627 ger DE-627 rakwb eng Feng, Zipei verfasserin aut Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Feng et al. 2015 Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. Tumor-infiltrating lymphocytes (TIL) (dpeaa)DE-He213 multispectral imaging (dpeaa)DE-He213 Adoptive T cell therapy (ACT) (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Immunoprofiling (dpeaa)DE-He213 Immunoscore (dpeaa)DE-He213 Immunotherapy biomarker (dpeaa)DE-He213 Puri, Sachin aut Moudgil, Tarsem aut Wood, William aut Hoyt, Clifford C. aut Wang, Chichung aut Urba, Walter J. aut Curti, Brendan D. aut Bifulco, Carlo B. aut Fox, Bernard A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 3(2015), 1 vom: 20. Okt. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:3 year:2015 number:1 day:20 month:10 https://dx.doi.org/10.1186/s40425-015-0091-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2015 1 20 10 |
spelling |
10.1186/s40425-015-0091-z doi (DE-627)SPR03642868X (SPR)s40425-015-0091-z-e DE-627 ger DE-627 rakwb eng Feng, Zipei verfasserin aut Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Feng et al. 2015 Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. Tumor-infiltrating lymphocytes (TIL) (dpeaa)DE-He213 multispectral imaging (dpeaa)DE-He213 Adoptive T cell therapy (ACT) (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Immunoprofiling (dpeaa)DE-He213 Immunoscore (dpeaa)DE-He213 Immunotherapy biomarker (dpeaa)DE-He213 Puri, Sachin aut Moudgil, Tarsem aut Wood, William aut Hoyt, Clifford C. aut Wang, Chichung aut Urba, Walter J. aut Curti, Brendan D. aut Bifulco, Carlo B. aut Fox, Bernard A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 3(2015), 1 vom: 20. Okt. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:3 year:2015 number:1 day:20 month:10 https://dx.doi.org/10.1186/s40425-015-0091-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2015 1 20 10 |
allfields_unstemmed |
10.1186/s40425-015-0091-z doi (DE-627)SPR03642868X (SPR)s40425-015-0091-z-e DE-627 ger DE-627 rakwb eng Feng, Zipei verfasserin aut Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Feng et al. 2015 Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. Tumor-infiltrating lymphocytes (TIL) (dpeaa)DE-He213 multispectral imaging (dpeaa)DE-He213 Adoptive T cell therapy (ACT) (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Immunoprofiling (dpeaa)DE-He213 Immunoscore (dpeaa)DE-He213 Immunotherapy biomarker (dpeaa)DE-He213 Puri, Sachin aut Moudgil, Tarsem aut Wood, William aut Hoyt, Clifford C. aut Wang, Chichung aut Urba, Walter J. aut Curti, Brendan D. aut Bifulco, Carlo B. aut Fox, Bernard A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 3(2015), 1 vom: 20. Okt. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:3 year:2015 number:1 day:20 month:10 https://dx.doi.org/10.1186/s40425-015-0091-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2015 1 20 10 |
allfieldsGer |
10.1186/s40425-015-0091-z doi (DE-627)SPR03642868X (SPR)s40425-015-0091-z-e DE-627 ger DE-627 rakwb eng Feng, Zipei verfasserin aut Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Feng et al. 2015 Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. Tumor-infiltrating lymphocytes (TIL) (dpeaa)DE-He213 multispectral imaging (dpeaa)DE-He213 Adoptive T cell therapy (ACT) (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Immunoprofiling (dpeaa)DE-He213 Immunoscore (dpeaa)DE-He213 Immunotherapy biomarker (dpeaa)DE-He213 Puri, Sachin aut Moudgil, Tarsem aut Wood, William aut Hoyt, Clifford C. aut Wang, Chichung aut Urba, Walter J. aut Curti, Brendan D. aut Bifulco, Carlo B. aut Fox, Bernard A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 3(2015), 1 vom: 20. Okt. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:3 year:2015 number:1 day:20 month:10 https://dx.doi.org/10.1186/s40425-015-0091-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2015 1 20 10 |
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10.1186/s40425-015-0091-z doi (DE-627)SPR03642868X (SPR)s40425-015-0091-z-e DE-627 ger DE-627 rakwb eng Feng, Zipei verfasserin aut Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Feng et al. 2015 Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. Tumor-infiltrating lymphocytes (TIL) (dpeaa)DE-He213 multispectral imaging (dpeaa)DE-He213 Adoptive T cell therapy (ACT) (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Immunoprofiling (dpeaa)DE-He213 Immunoscore (dpeaa)DE-He213 Immunotherapy biomarker (dpeaa)DE-He213 Puri, Sachin aut Moudgil, Tarsem aut Wood, William aut Hoyt, Clifford C. aut Wang, Chichung aut Urba, Walter J. aut Curti, Brendan D. aut Bifulco, Carlo B. aut Fox, Bernard A. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 3(2015), 1 vom: 20. Okt. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:3 year:2015 number:1 day:20 month:10 https://dx.doi.org/10.1186/s40425-015-0091-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2015 1 20 10 |
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Feng, Zipei misc Tumor-infiltrating lymphocytes (TIL) misc multispectral imaging misc Adoptive T cell therapy (ACT) misc Immunotherapy misc Melanoma misc Immunoprofiling misc Immunoscore misc Immunotherapy biomarker Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma |
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Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma Tumor-infiltrating lymphocytes (TIL) (dpeaa)DE-He213 multispectral imaging (dpeaa)DE-He213 Adoptive T cell therapy (ACT) (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Immunoprofiling (dpeaa)DE-He213 Immunoscore (dpeaa)DE-He213 Immunotherapy biomarker (dpeaa)DE-He213 |
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Feng, Zipei Puri, Sachin Moudgil, Tarsem Wood, William Hoyt, Clifford C. Wang, Chichung Urba, Walter J. Curti, Brendan D. Bifulco, Carlo B. Fox, Bernard A. |
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Elektronische Aufsätze |
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Feng, Zipei |
doi_str_mv |
10.1186/s40425-015-0091-z |
title_sort |
multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma |
title_auth |
Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma |
abstract |
Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. © Feng et al. 2015 |
abstractGer |
Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. © Feng et al. 2015 |
abstract_unstemmed |
Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of $ CD8^{+} $ T cells alone was insufficient to predict successful TIL generation, the $ CD8^{+} $ to $ FoxP3^{+} $ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of $ CD8^{+} $:PD-$ L1^{+} $ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. © Feng et al. 2015 |
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title_short |
Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma |
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https://dx.doi.org/10.1186/s40425-015-0091-z |
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Puri, Sachin Moudgil, Tarsem Wood, William Hoyt, Clifford C. Wang, Chichung Urba, Walter J. Curti, Brendan D. Bifulco, Carlo B. Fox, Bernard A. |
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Puri, Sachin Moudgil, Tarsem Wood, William Hoyt, Clifford C. Wang, Chichung Urba, Walter J. Curti, Brendan D. Bifulco, Carlo B. Fox, Bernard A. |
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