Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1783658214891454464
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
work_keys_str_mv AT strippolisabino examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT fanizziannarita examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT negriantonio examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT quaresminidavide examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT nardoneannalisa examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT armenioandrea examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT sciacovelliangelamonica examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT massafraraffaella examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT derisiivana examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT detulliogiacoma examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT albanoanna examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma
AT guidamichele examiningtherelationshipbetweencirculatingcd4cd8doublenegativetcellsandoutcomesofimmunocheckpointinhibitortherapylookingforbiomarkersandtherapeutictargetsinmetastaticmelanoma