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Here, we address the dilemma of using corticosteroids for the treatment of irAEs induced by ICB. ICB augments neoantigen-specific CD8+ T cell responses, resulting in tumor regression. In our model, simultaneous, but not late, administration of corticosteroids impaired antitumor responses with reduction of CD8+ T cell proliferation. Secondary challenge using tumors with\/without the neoantigen showed selective progression in tumors lacking the neoantigen when corticosteroids were administered. Corticosteroids decreased low- but not high-affinity memory T cells by suppressing fatty acid metabolism essential for memory T cells. In a small cohort of human melanoma patients, overall survival was shorter after treatment with CTLA-4 blockade in patients who received early corticosteroids or had low tumor mutation burden. Together, low-affinity memory T cells are dominantly suppressed by corticosteroids, necessitating careful and thoughtful corticosteroid use.<\/jats:p>","DOI":"10.1084\/jem.20190738","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T15:05:12Z","timestamp":1568905512000},"page":"2701-2713","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":120,"title":["Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids"],"prefix":"10.1084","volume":"216","author":[{"given":"Akihiro","family":"Tokunaga","sequence":"first","affiliation":[{"name":"Division of Cancer Immunology, Research Institute\/Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan 1"},{"name":"Oncology Research and Development Unit, Kyowa Kirin Co., Ltd., Shizuoka, Japan 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Maeda","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunology, Research Institute\/Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6422-2997","authenticated-orcid":true,"given":"Allison Betof","family":"Warner","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy, Swim Across America-Ludwig Collaborative Lab, Memorial Sloan-Kettering Cancer Center, New York, NY 4"},{"name":"Weill Cornell Medical College, New York, NY 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine S.","family":"Panageas","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Togashi","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunology, Research Institute\/Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Sakai","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunology, Research Institute\/Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6718-2222","authenticated-orcid":true,"given":"Jedd D.","family":"Wolchok","sequence":"additional","affiliation":[{"name":"Parker Institute for Cancer Immunotherapy, Swim Across America-Ludwig Collaborative Lab, Memorial Sloan-Kettering Cancer Center, New York, NY 4"},{"name":"Weill Cornell Medical College, New York, NY 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-9807","authenticated-orcid":true,"given":"Hiroyoshi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Division of Cancer Immunology, Research Institute\/Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan 1"},{"name":"Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"2023072610413208400_bib1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev.immunol.18.1.309","article-title":"Glucocorticoids in T cell development and function","volume":"18","author":"Ashwell","year":"2000","journal-title":"Annu. 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