{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T07:53:16Z","timestamp":1762069996810,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ALP Institute for Regenerative Medicine Inc.","award":["JPMJOP1722","JP19K07330"],"award-info":[{"award-number":["JPMJOP1722","JP19K07330"]}]},{"name":"Program on Open Innovation Platform with Enterprises, Research Institutes, and Academia of the JST","award":["JPMJOP1722","JP19K07330"],"award-info":[{"award-number":["JPMJOP1722","JP19K07330"]}]},{"name":"JSPS KAKENHI","award":["JPMJOP1722","JP19K07330"],"award-info":[{"award-number":["JPMJOP1722","JP19K07330"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8+ T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms\u2019 Tumor 1 (WT1) antigen over the disease course (two points at MPE1st and 2nd, two months after MPE1st). Epithelial cell adhesion molecule (EpCAM)+ cancer cells (PD-L1\u2212 or T cell immunoglobulin mucin-3, TIM-3\u2212), both PD-1 or TIM-3 positive CD8+ T cells, and CD14+CD68+CD163+TIM-3+ macrophages increased from the MPE1st to MPE2nd. The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8+ T cells and IFN-\u03b3 secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (TCM) of WT1-CTLs was decreased. On the other hand, CD8+ T cells in response to SMAD4P130L, which is homogeneously expressed in EpCAM+ cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8+ T cell response to SMAD4P130L was diminished following remarkably decreased numbers of CD8+ TCM in MPE samples. In conclusion, CD8+ T cells responding to WT1 or SMAD4P130L neoantigen expressed in EpCAM+ pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment.<\/jats:p>","DOI":"10.3390\/ijms232012177","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T20:53:29Z","timestamp":1665608009000},"page":"12177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0804-1045","authenticated-orcid":false,"given":"Terutsugu","family":"Koya","sequence":"first","affiliation":[{"name":"Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-7962","authenticated-orcid":false,"given":"Yo","family":"Niida","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7424-4548","authenticated-orcid":false,"given":"Misa","family":"Togi","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-4510","authenticated-orcid":false,"given":"Takuya","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-3481","authenticated-orcid":false,"given":"Hiroki","family":"Ura","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-8111","authenticated-orcid":false,"given":"Sumihito","family":"Togi","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Tomohisa","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Stem Cell Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2662-0024","authenticated-orcid":false,"given":"Sohsuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruo","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Graduate School of Medicine, Osaka University, Suita 565-0871, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0397-4348","authenticated-orcid":false,"given":"Shigeo","family":"Koido","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Jikei University School of Medicine, Kashiwa 277-8567, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-6912","authenticated-orcid":false,"given":"Shigetaka","family":"Shimodaira","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Center for Regenerative medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Division of Stem Cell Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-Line Nivolumab plus Ipilimumab in Unresectable Malignant Pleural Mesothelioma (CheckMate 743): A Multicentre, Randomised, Open-Label, Phase 3 Trial","volume":"397","author":"Baas","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.lungcan.2016.04.015","article-title":"Precision Immunotherapy; Dynamics in the Cellular Profile of Pleural Effusions in Malignant Mesothelioma Patients","volume":"107","author":"Lievense","year":"2017","journal-title":"Lung Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.25259\/CMAS_02_09_2021","article-title":"Metastatic Carcinoma in 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