Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy
IntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a det...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197630/full |
| _version_ | 1797738259732758528 |
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| author | Maria Luigia Carbone Alessia Capone Marika Guercio Sofia Reddel Domenico Alessandro Silvestris Daniela Lulli Carmela Ramondino Daniele Peluso Concetta Quintarelli Concetta Quintarelli Elisabetta Volpe Cristina Maria Failla |
| author_facet | Maria Luigia Carbone Alessia Capone Marika Guercio Sofia Reddel Domenico Alessandro Silvestris Daniela Lulli Carmela Ramondino Daniele Peluso Concetta Quintarelli Concetta Quintarelli Elisabetta Volpe Cristina Maria Failla |
| author_sort | Maria Luigia Carbone |
| collection | DOAJ |
| description | IntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor. |
| first_indexed | 2024-03-12T13:40:15Z |
| format | Article |
| id | doaj.art-7726efa99086462895f0587522f4d224 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T13:40:15Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7726efa99086462895f0587522f4d2242023-08-23T19:28:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.11976301197630Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapyMaria Luigia Carbone0Alessia Capone1Marika Guercio2Sofia Reddel3Domenico Alessandro Silvestris4Daniela Lulli5Carmela Ramondino6Daniele Peluso7Concetta Quintarelli8Concetta Quintarelli9Elisabetta Volpe10Cristina Maria Failla11Laboratory of Experimental Immunology, Istituto Dermopatico dell’Immacolata (IDI)-IRCCS, Rome, ItalyLaboratory of Molecular Neuroimmunology, Santa Lucia Foundation-IRCCS, Rome, ItalyDepartment of Oncology-Hematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, ItalyDepartment of Oncology-Hematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, ItalyDepartment of Oncology-Hematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, ItalyLaboratory of Experimental Immunology, Istituto Dermopatico dell’Immacolata (IDI)-IRCCS, Rome, ItalyLaboratory of Experimental Immunology, Istituto Dermopatico dell’Immacolata (IDI)-IRCCS, Rome, ItalyDepartment of Biology, University “Tor Vergata”, Rome, ItalyDepartment of Oncology-Hematology, and Cell and Gene Therapy, Bambino Gesù Children Hospital, IRCCS, Rome, ItalyDepartment of Clinical Medicine and Surgery, University of Naples Federico II, Naples, ItalyLaboratory of Molecular Neuroimmunology, Santa Lucia Foundation-IRCCS, Rome, ItalyLaboratory of Experimental Immunology, Istituto Dermopatico dell’Immacolata (IDI)-IRCCS, Rome, ItalyIntroductionImmunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response. MethodsTo better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.Results and discussionStratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56bright, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197630/fullmelanomaimmunotherapyvitiligobiomarkersT-cell receptor |
| spellingShingle | Maria Luigia Carbone Alessia Capone Marika Guercio Sofia Reddel Domenico Alessandro Silvestris Daniela Lulli Carmela Ramondino Daniele Peluso Concetta Quintarelli Concetta Quintarelli Elisabetta Volpe Cristina Maria Failla Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy Frontiers in Immunology melanoma immunotherapy vitiligo biomarkers T-cell receptor |
| title | Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy |
| title_full | Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy |
| title_fullStr | Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy |
| title_full_unstemmed | Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy |
| title_short | Insight into immune profile associated with vitiligo onset and anti-tumoral response in melanoma patients receiving anti-PD-1 immunotherapy |
| title_sort | insight into immune profile associated with vitiligo onset and anti tumoral response in melanoma patients receiving anti pd 1 immunotherapy |
| topic | melanoma immunotherapy vitiligo biomarkers T-cell receptor |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1197630/full |
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