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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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/406 |
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| author | Sabino Strippoli Annarita Fanizzi Antonio Negri Davide Quaresmini Annalisa Nardone Andrea Armenio Angela Monica Sciacovelli Raffaella Massafra Ivana De Risi Giacoma De Tullio Anna Albano Michele Guida |
| author_facet | Sabino Strippoli Annarita Fanizzi Antonio Negri Davide Quaresmini Annalisa Nardone Andrea Armenio Angela Monica Sciacovelli Raffaella Massafra Ivana De Risi Giacoma De Tullio Anna Albano Michele Guida |
| author_sort | Sabino Strippoli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T00:50:28Z |
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| id | doaj.art-52c5804d7cb440e2bb5654d6e9c2d1c6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T00:50:28Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-52c5804d7cb440e2bb5654d6e9c2d1c62023-12-11T17:14:06ZengMDPI AGCells2073-44092021-02-0110240610.3390/cells10020406Examining 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 MelanomaSabino Strippoli0Annarita Fanizzi1Antonio Negri2Davide Quaresmini3Annalisa Nardone4Andrea Armenio5Angela Monica Sciacovelli6Raffaella Massafra7Ivana De Risi8Giacoma De Tullio9Anna Albano10Michele Guida11Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRadiotherapy Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyUnit of Hematology and Cell Therapy, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRare Tumors and Melanoma Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRadiotherapy Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyDepartment of Plastic Surgery, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRare Tumors and Melanoma Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRadiotherapy Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRare Tumors and Melanoma Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyUnit of Hematology and Cell Therapy, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRare Tumors and Melanoma Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyRare Tumors and Melanoma Unit, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, ItalyBackground: 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.https://www.mdpi.com/2073-4409/10/2/406double negative T cellscheckpoint inhibitorsmelanomaimmunotherapy resistance |
| spellingShingle | Sabino Strippoli Annarita Fanizzi Antonio Negri Davide Quaresmini Annalisa Nardone Andrea Armenio Angela Monica Sciacovelli Raffaella Massafra Ivana De Risi Giacoma De Tullio Anna Albano Michele Guida 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 Cells double negative T cells checkpoint inhibitors melanoma immunotherapy resistance |
| 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 | double negative T cells checkpoint inhibitors melanoma immunotherapy resistance |
| url | https://www.mdpi.com/2073-4409/10/2/406 |
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