Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma

Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment...
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Autor*in:	Sabino Strippoli [verfasserIn] Annarita Fanizzi [verfasserIn] Antonio Negri [verfasserIn] Davide Quaresmini [verfasserIn] Annalisa Nardone [verfasserIn] Andrea Armenio [verfasserIn] Angela Monica Sciacovelli [verfasserIn] Raffaella Massafra [verfasserIn] Ivana De Risi [verfasserIn] Giacoma De Tullio [verfasserIn] Anna Albano [verfasserIn] Michele Guida [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	double negative T cells checkpoint inhibitors melanoma immunotherapy resistance

Übergeordnetes Werk:	In: Cells - MDPI AG, 2012, 10(2021), 2, p 406
Übergeordnetes Werk:	volume:10 ; year:2021 ; number:2, p 406

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cells10020406

Katalog-ID:	DOAJ074124382

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allfields	10.3390/cells10020406 doi (DE-627)DOAJ074124382 (DE-599)DOAJ52c5804d7cb440e2bb5654d6e9c2d1c6 DE-627 ger DE-627 rakwb eng QH573-671 Sabino Strippoli verfasserin aut Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted. double negative T cells checkpoint inhibitors melanoma immunotherapy resistance Cytology Annarita Fanizzi verfasserin aut Antonio Negri verfasserin aut Davide Quaresmini verfasserin aut Annalisa Nardone verfasserin aut Andrea Armenio verfasserin aut Angela Monica Sciacovelli verfasserin aut Raffaella Massafra verfasserin aut Ivana De Risi verfasserin aut Giacoma De Tullio verfasserin aut Anna Albano verfasserin aut Michele Guida verfasserin aut In Cells MDPI AG, 2012 10(2021), 2, p 406 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:2, p 406 https://doi.org/10.3390/cells10020406 kostenfrei https://doaj.org/article/52c5804d7cb440e2bb5654d6e9c2d1c6 kostenfrei https://www.mdpi.com/2073-4409/10/2/406 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 10 2021 2, p 406
spelling	10.3390/cells10020406 doi (DE-627)DOAJ074124382 (DE-599)DOAJ52c5804d7cb440e2bb5654d6e9c2d1c6 DE-627 ger DE-627 rakwb eng QH573-671 Sabino Strippoli verfasserin aut Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted. double negative T cells checkpoint inhibitors melanoma immunotherapy resistance Cytology Annarita Fanizzi verfasserin aut Antonio Negri verfasserin aut Davide Quaresmini verfasserin aut Annalisa Nardone verfasserin aut Andrea Armenio verfasserin aut Angela Monica Sciacovelli verfasserin aut Raffaella Massafra verfasserin aut Ivana De Risi verfasserin aut Giacoma De Tullio verfasserin aut Anna Albano verfasserin aut Michele Guida verfasserin aut In Cells MDPI AG, 2012 10(2021), 2, p 406 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:2, p 406 https://doi.org/10.3390/cells10020406 kostenfrei https://doaj.org/article/52c5804d7cb440e2bb5654d6e9c2d1c6 kostenfrei https://www.mdpi.com/2073-4409/10/2/406 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 10 2021 2, p 406
allfields_unstemmed	10.3390/cells10020406 doi (DE-627)DOAJ074124382 (DE-599)DOAJ52c5804d7cb440e2bb5654d6e9c2d1c6 DE-627 ger DE-627 rakwb eng QH573-671 Sabino Strippoli verfasserin aut Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted. double negative T cells checkpoint inhibitors melanoma immunotherapy resistance Cytology Annarita Fanizzi verfasserin aut Antonio Negri verfasserin aut Davide Quaresmini verfasserin aut Annalisa Nardone verfasserin aut Andrea Armenio verfasserin aut Angela Monica Sciacovelli verfasserin aut Raffaella Massafra verfasserin aut Ivana De Risi verfasserin aut Giacoma De Tullio verfasserin aut Anna Albano verfasserin aut Michele Guida verfasserin aut In Cells MDPI AG, 2012 10(2021), 2, p 406 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:2, p 406 https://doi.org/10.3390/cells10020406 kostenfrei https://doaj.org/article/52c5804d7cb440e2bb5654d6e9c2d1c6 kostenfrei https://www.mdpi.com/2073-4409/10/2/406 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 10 2021 2, p 406
allfieldsGer	10.3390/cells10020406 doi (DE-627)DOAJ074124382 (DE-599)DOAJ52c5804d7cb440e2bb5654d6e9c2d1c6 DE-627 ger DE-627 rakwb eng QH573-671 Sabino Strippoli verfasserin aut Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted. double negative T cells checkpoint inhibitors melanoma immunotherapy resistance Cytology Annarita Fanizzi verfasserin aut Antonio Negri verfasserin aut Davide Quaresmini verfasserin aut Annalisa Nardone verfasserin aut Andrea Armenio verfasserin aut Angela Monica Sciacovelli verfasserin aut Raffaella Massafra verfasserin aut Ivana De Risi verfasserin aut Giacoma De Tullio verfasserin aut Anna Albano verfasserin aut Michele Guida verfasserin aut In Cells MDPI AG, 2012 10(2021), 2, p 406 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:2, p 406 https://doi.org/10.3390/cells10020406 kostenfrei https://doaj.org/article/52c5804d7cb440e2bb5654d6e9c2d1c6 kostenfrei https://www.mdpi.com/2073-4409/10/2/406 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 10 2021 2, p 406
allfieldsSound	10.3390/cells10020406 doi (DE-627)DOAJ074124382 (DE-599)DOAJ52c5804d7cb440e2bb5654d6e9c2d1c6 DE-627 ger DE-627 rakwb eng QH573-671 Sabino Strippoli verfasserin aut Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted. double negative T cells checkpoint inhibitors melanoma immunotherapy resistance Cytology Annarita Fanizzi verfasserin aut Antonio Negri verfasserin aut Davide Quaresmini verfasserin aut Annalisa Nardone verfasserin aut Andrea Armenio verfasserin aut Angela Monica Sciacovelli verfasserin aut Raffaella Massafra verfasserin aut Ivana De Risi verfasserin aut Giacoma De Tullio verfasserin aut Anna Albano verfasserin aut Michele Guida verfasserin aut In Cells MDPI AG, 2012 10(2021), 2, p 406 (DE-627)718622081 (DE-600)2661518-6 20734409 nnns volume:10 year:2021 number:2, p 406 https://doi.org/10.3390/cells10020406 kostenfrei https://doaj.org/article/52c5804d7cb440e2bb5654d6e9c2d1c6 kostenfrei https://www.mdpi.com/2073-4409/10/2/406 kostenfrei https://doaj.org/toc/2073-4409 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 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 10 2021 2, p 406
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callnumber-first	Q - Science
author	Sabino Strippoli
spellingShingle	Sabino Strippoli misc QH573-671 misc double negative T cells misc checkpoint inhibitors misc melanoma misc immunotherapy resistance misc Cytology Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma
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topic_title	QH573-671 Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma double negative T cells checkpoint inhibitors melanoma immunotherapy resistance
topic	misc QH573-671 misc double negative T cells misc checkpoint inhibitors misc melanoma misc immunotherapy resistance misc Cytology
topic_unstemmed	misc QH573-671 misc double negative T cells misc checkpoint inhibitors misc melanoma misc immunotherapy resistance misc Cytology
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title	Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma
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title_full	Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma
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title_sort	examining the relationship between circulating cd4− cd8− double-negative t cells and outcomes of immuno-checkpoint inhibitor therapy—looking for biomarkers and therapeutic targets in metastatic melanoma
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title_auth	Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma
abstract	Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted.
abstractGer	Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted.
abstract_unstemmed	Background: The role of circulating CD4<b<−</b</CD8<b<−</b< double-negative T cells (DNTs) in the immune response to melanoma is poorly understood, as are the effects of checkpoint inhibitors on T cell subpopulations. Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted.
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title_short	Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma
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Methods: We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Results: Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. Conclusions: DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. 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Examining the Relationship between Circulating CD4− CD8− Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy—Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma

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