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Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment. We found that, in addition to the PD-L1 (p = 0.03), expression levels of PD-1 ligand-2 (PD-L2), granzyme A (GZMA) and human leukocyte antigen-A (HLA-A) in the pre-treatment tumors were significantly higher (p = 0.04, p = 0.01 and p = 0.006, respectively) in responders (n = 5) than in non-responders (n = 8). With nivolumab treatment, tumors in responders exhibited a substantial increase of CD8, GZMA and perforin 1 (PRF1) expression levels as well as increased ratio of TBX21/GATA3, suggesting dominancy of helper T cell type 1 (Th1) response to type 2 (Th2) response. T cell receptor \u03b2 (TCR-\u03b2) repertoire analysis revealed oligoclonal expansion of tumor-infiltrating T lymphocytes (TILs) in the tumor tissues of the responders. Our findings suggest that melanoma harboring high PD-1 ligands (PD-L1 and PD-L2), GZMA and HLA-A expression may respond preferentially to nivolumab treatment, which can enhance Th1-skewed cellular immunity with oligoclonal expansion of TILs.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7\uff08\u30b3\u30f3\u30c6\u30f3\u30c4\u306e\u7a2e\u985e\uff09", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "\u5f15\u7528", "attribute_value_mlt": [{"subitem_description": "ONCOIMMUNOLOGY.5(9):e1204507(2016)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "\u4fe1\u5dde\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7\u3078\u306e\u30ea\u30f3\u30af", "attribute_value_mlt": [{"subitem_link_text": "Okuyama, Ryuhei", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.ZpfNHFSF.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000385528200006"}]}, "item_6_publisher_4": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "TAYLOR \u0026 FRANCIS INC"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "27757299"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://www.ncbi.nlm.nih.gov/pubmed/27757299", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1080/2162402X.2016.1204507"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1080/2162402X.2016.1204507", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "\u00a9 2016 The Author(s). Published with license by Taylor \u0026 Francis Group, LLC\u00a9 Hiroyuki Inoue, Jae-Hyun Park, Kazuma Kiyotani, Makda Zewde, Azusa Miyashita, Masatoshi Jinnin, Yukiko Kiniwa, Ryuhei Okuyama, Ryota Tanaka, Yasuhiro Fujisawa, Hiroshi Kato, Akimichi Morita, Jun Asai, Norito Katoh, Kenji Yokota, Masashi Akiyama, Hironobu Ihn, Satoshi Fukushima, and Yusuke Nakamura. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted."}]}, "item_6_select_64": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "2162-4011", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "2162-4011", "subitem_source_identifier_type": "PISSN"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Metastatic melanoma; nivolumab; oligoclonal T cell expansion; PD-1; T-cell receptor sequencing"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "TUMOR-INFILTRATING LYMPHOCYTES; ANTI-PD-L1 ANTIBODY; CANCER; REPERTOIRE; BLOCKADE; IMMUNOTHERAPY; LIGANDS; SAFETY"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Immune checkpoint inhibitors blocking the interaction between programmed death-1 (PD-1) and PD-1 ligand-1 (PD-L1) are revolutionizing the cancer immunotherapies with durable clinical responses. Although high expression of PD-L1 in tumor tissues has been implicated to correlate with the better response to the anti-PD-1 therapies, this association has been controversial. In this study, to characterize immune microenvironment in tumors, we examined mRNA levels of immune-related genes and characterized T cell repertoire in the tumors of 13 melanoma patients before and after nivolumab treatment. We found that, in addition to the PD-L1 (p = 0.03), expression levels of PD-1 ligand-2 (PD-L2), granzyme A (GZMA) and human leukocyte antigen-A (HLA-A) in the pre-treatment tumors were significantly higher (p = 0.04, p = 0.01 and p = 0.006, respectively) in responders (n = 5) than in non-responders (n = 8). With nivolumab treatment, tumors in responders exhibited a substantial increase of CD8, GZMA and perforin 1 (PRF1) expression levels as well as increased ratio of TBX21/GATA3, suggesting dominancy of helper T cell type 1 (Th1) response to type 2 (Th2) response. T cell receptor (TCR-) repertoire analysis revealed oligoclonal expansion of tumor-infiltrating T lymphocytes (TILs) in the tumor tissues of the responders. Our findings suggest that melanoma harboring high PD-1 ligands (PD-L1 and PD-L2), GZMA and HLA-A expression may respond preferentially to nivolumab treatment, which can enhance Th1-skewed cellular immunity with oligoclonal expansion of TILs."}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Inoue, Hiroyuki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106645", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Park, Jae-Hyun", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106646", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kiyotani, Kazuma", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106647", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Zewde, Makda", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106648", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Miyashita, Azusa", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106649", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Jinnin, Masatoshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106650", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kiniwa, Yukiko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106651", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Okuyama, Ryuhei", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106652", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tanaka, Ryota", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106653", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Fujisawa, Yasuhiro", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106654", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kato, Hiroshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106655", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Morita, Akimichi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106656", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Asai, Jun", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106657", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Katoh, Norito", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106658", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Yokota, Kenji", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106659", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Akiyama, Masashi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106660", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ihn, Hironobu", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106661", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Fukushima, Satoshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106662", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nakamura, Yusuke", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "106663", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2021-09-08"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "Intratumoral expression levels of PD L1 GZMA and HLA A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic.pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "\u00a9 2016 The Author(s). 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