PMID- 32554608 OWN - NLM STAT- MEDLINE DCOM- 20210820 LR - 20240426 IS - 2051-1426 (Electronic) IS - 2051-1426 (Linking) VI - 8 IP - 1 DP - 2020 Jun TI - 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. LID - 10.1136/jitc-2019-000209 [doi] LID - e000209 AB - 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. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Ladanyi, Andrea AU - Ladanyi A AUID- ORCID: 0000-0001-9304-8473 AD - Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest, Hungary ladanyi@oncol.hu. FAU - Papp, Eszter AU - Papp E AD - Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest, Hungary. FAU - Mohos, Anita AU - Mohos A AD - 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. FAU - Balatoni, Timea AU - Balatoni T AD - Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary. FAU - Liszkay, Gabriella AU - Liszkay G AD - Department of Oncodermatology, National Institute of Oncology, Budapest, Hungary. FAU - Olah, Judit AU - Olah J AD - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. FAU - Varga, Anita AU - Varga A AD - Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. FAU - Lengyel, Zsuzsanna AU - Lengyel Z AD - Department of Dermatology, Venerology and Oncodermatology, University of Pecs Clinical Center, Pecs, Hungary. FAU - Emri, Gabriella AU - Emri G AD - Department of Dermatology, University of Debrecen Medical School and Health Science Center, Debrecen, Hungary. FAU - Ferrone, Soldano AU - Ferrone S AUID- ORCID: 0000-0003-2900-8834 AD - Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - R01 DE028172/DE/NIDCR NIH HHS/United States GR - R03 CA219603/CA/NCI NIH HHS/United States GR - R03 CA253319/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - J Immunother Cancer JT - Journal for immunotherapy of cancer JID - 101620585 RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Ipilimumab) SB - IM MH - Antineoplastic Agents, Immunological/pharmacology/*therapeutic use MH - Female MH - Histocompatibility Antigens Class I/*metabolism MH - Humans MH - Ipilimumab/pharmacology/*therapeutic use MH - Male MH - Melanoma/*drug therapy/mortality MH - Neoplasm Metastasis MH - Skin Neoplasms/*drug therapy/mortality MH - Survival Analysis PMC - PMC7304850 OTO - NOTNLM OT - HLA OT - immunology OT - oncology OT - tumors COIS- Competing interests: TB has received speaker honoraria and financial support for attending symposia from Bristol-Myers Squibb, MSD Sharp & Dohme (MSD), Novartis, and Roche. GL is on the advisory board and has received honoraria for speaking at conferences as well as financial support for educational programs from Bristol-Myers Squibb, GlaxoSmithKline, MSD, Novartis, and Roche. JO has acted as a speaker of symposia and consultant for Bristol-Myers Squibb, MSD, Novartis and Roche. ZL has received speaker honoraria from Bristol-Myers Squibb, MSD, Novartis, and Roche. GE has received speaker honoraria from Bristol-Myers Squibb, MSD, and Roche. SF has received a research grant from Merck. EDAT- 2020/06/20 06:00 MHDA- 2021/08/21 06:00 PMCR- 2020/06/17 CRDT- 2020/06/20 06:00 PHST- 2020/05/02 00:00 [accepted] PHST- 2020/06/20 06:00 [entrez] PHST- 2020/06/20 06:00 [pubmed] PHST- 2021/08/21 06:00 [medline] PHST- 2020/06/17 00:00 [pmc-release] AID - jitc-2019-000209 [pii] AID - 10.1136/jitc-2019-000209 [doi] PST - ppublish SO - J Immunother Cancer. 2020 Jun;8(1):e000209. doi: 10.1136/jitc-2019-000209.