Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma
Background The clinical response to immune checkpoint inhibitors (ICIs) in only part of the treated patients, in conjunction with the potentially serious side effects associated with this type of therapy, has emphasized the need to identify biomarkers to select patients who may benefit from ICI trea...
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000209.full |
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| author | Timea Balatoni Soldano Ferrone Judit Olah Andrea Ladányi Eszter Papp Anita Mohos Anita Varga Zsuzsanna Lengyel Gabriella Emri |
| author_facet | Timea Balatoni Soldano Ferrone Judit Olah Andrea Ladányi Eszter Papp Anita Mohos Anita Varga Zsuzsanna Lengyel Gabriella Emri |
| author_sort | Timea Balatoni |
| collection | DOAJ |
| description | Background The clinical response to immune checkpoint inhibitors (ICIs) in only part of the treated patients, in conjunction with the potentially serious side effects associated with this type of therapy, has emphasized the need to identify biomarkers to select patients who may benefit from ICI treatment. The aim of our study was to test human leukocyte antigen (HLA) class I and II expression in melanoma metastases as potential biomarkers of response to ipilimumab and survival in patients with metastatic melanoma, since these molecules play a crucial role in the interactions of malignant cells with host’s immune system.Materials and methods HLA class I and II antigen expression level in pretreatment surgical tissue samples (50 lymph node and 35 cutaneous or subcutaneous metastases) from 30 patients was analyzed by immunohistochemical staining with monoclonal antibodies. Expression levels were correlated to intratumoral density of lymphocytes expressing cluster of differentiation (CD)8, CD45RO, CD4, forkhead box P3 (FOXP3) and/or programmed cell death protein 1 (PD-1), to clinical response to treatment, and to patients’ survival.Results HLA class I antigen expression level in lymph node metastases, but not in cutaneous or subcutaneous metastases was significantly correlated to density of CD8+ and CD45RO+ T cells and of lymphocytes expressing PD-1, as well as to clinical response and to patients’ survival.Conclusions Our results corroborate the role of HLA class I expression level (alone or in combination with T-cell density values) as a predictive biomarker of response to ipilimumab in patients with melanoma. In addition, our results show that this association is influenced by the anatomic site of the metastasis used to measure the HLA class I antigen expression level. |
| format | Article |
| id | doaj-art-d9749f49fa9b4b4381ea299992be4d47 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d9749f49fa9b4b4381ea299992be4d472025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000209Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanomaTimea Balatoni0Soldano Ferrone1Judit Olah2Andrea Ladányi3Eszter Papp4Anita Mohos5Anita Varga6Zsuzsanna Lengyel7Gabriella Emri8Aff2 grid.419617.c0000000106678064OncodermatologyNational Institute of Oncology Budapest HungaryDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA4 Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary1 Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest, Hungary1 Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest, Hungary2 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary4 Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary5 Department of Dermatology, Venerology and Oncodermatology, University of Pécs Clinical Center, Pécs, Hungary6 Department of Dermatology, University of Debrecen Medical School and Health Science Center, Debrecen, HungaryBackground The clinical response to immune checkpoint inhibitors (ICIs) in only part of the treated patients, in conjunction with the potentially serious side effects associated with this type of therapy, has emphasized the need to identify biomarkers to select patients who may benefit from ICI treatment. The aim of our study was to test human leukocyte antigen (HLA) class I and II expression in melanoma metastases as potential biomarkers of response to ipilimumab and survival in patients with metastatic melanoma, since these molecules play a crucial role in the interactions of malignant cells with host’s immune system.Materials and methods HLA class I and II antigen expression level in pretreatment surgical tissue samples (50 lymph node and 35 cutaneous or subcutaneous metastases) from 30 patients was analyzed by immunohistochemical staining with monoclonal antibodies. Expression levels were correlated to intratumoral density of lymphocytes expressing cluster of differentiation (CD)8, CD45RO, CD4, forkhead box P3 (FOXP3) and/or programmed cell death protein 1 (PD-1), to clinical response to treatment, and to patients’ survival.Results HLA class I antigen expression level in lymph node metastases, but not in cutaneous or subcutaneous metastases was significantly correlated to density of CD8+ and CD45RO+ T cells and of lymphocytes expressing PD-1, as well as to clinical response and to patients’ survival.Conclusions Our results corroborate the role of HLA class I expression level (alone or in combination with T-cell density values) as a predictive biomarker of response to ipilimumab in patients with melanoma. In addition, our results show that this association is influenced by the anatomic site of the metastasis used to measure the HLA class I antigen expression level.https://jitc.bmj.com/content/8/1/e000209.full |
| spellingShingle | Timea Balatoni Soldano Ferrone Judit Olah Andrea Ladányi Eszter Papp Anita Mohos Anita Varga Zsuzsanna Lengyel Gabriella Emri Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma Journal for ImmunoTherapy of Cancer |
| title | Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma |
| title_full | Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma |
| title_fullStr | Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma |
| title_full_unstemmed | Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma |
| title_short | Role of the anatomic site in the association of HLA class I antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma |
| title_sort | role of the anatomic site in the association of hla class i antigen expression level in metastases with clinical response to ipilimumab therapy in patients with melanoma |
| url | https://jitc.bmj.com/content/8/1/e000209.full |
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