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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
Background: The role of circulating CD4−/CD8− 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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920027/ https://www.ncbi.nlm.nih.gov/pubmed/33669266 http://dx.doi.org/10.3390/cells10020406 |
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author | Strippoli, Sabino Fanizzi, Annarita Negri, Antonio Quaresmini, Davide Nardone, Annalisa Armenio, Andrea Sciacovelli, Angela Monica Massafra, Raffaella De Risi, Ivana De Tullio, Giacoma Albano, Anna Guida, Michele |
author_facet | Strippoli, Sabino Fanizzi, Annarita Negri, Antonio Quaresmini, Davide Nardone, Annalisa Armenio, Andrea Sciacovelli, Angela Monica Massafra, Raffaella De Risi, Ivana De Tullio, Giacoma Albano, Anna Guida, Michele |
author_sort | Strippoli, Sabino |
collection | PubMed |
description | Background: The role of circulating CD4−/CD8− 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. |
format | Online Article Text |
id | pubmed-7920027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79200272021-03-02 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 Strippoli, Sabino Fanizzi, Annarita Negri, Antonio Quaresmini, Davide Nardone, Annalisa Armenio, Andrea Sciacovelli, Angela Monica Massafra, Raffaella De Risi, Ivana De Tullio, Giacoma Albano, Anna Guida, Michele Cells Article Background: The role of circulating CD4−/CD8− 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. MDPI 2021-02-16 /pmc/articles/PMC7920027/ /pubmed/33669266 http://dx.doi.org/10.3390/cells10020406 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Strippoli, Sabino Fanizzi, Annarita Negri, Antonio Quaresmini, Davide Nardone, Annalisa Armenio, Andrea Sciacovelli, Angela Monica Massafra, Raffaella De Risi, Ivana De Tullio, Giacoma Albano, Anna Guida, Michele 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 |
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 |
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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
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 |
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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920027/ https://www.ncbi.nlm.nih.gov/pubmed/33669266 http://dx.doi.org/10.3390/cells10020406 |
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