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We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti\u2013PD-1 antibody (\u03b1PD-1); thus, we examined PDAC vaccine or radiation therapy (RT) as T cell priming mechanisms together with BMS-687681, a dual antagonist of CCR2 and CCR5 (CCR2\/5i), in combination with \u03b1PD-1 as new treatment strategies. Using PDAC mouse models, we demonstrated that RT followed by \u03b1PD-1 and prolonged treatment with CCR2\/5i conferred better antitumor efficacy than other combination treatments tested. The combination of RT + \u03b1PD-1 + CCR2\/5i enhanced intratumoral effector and memory T cell infiltration but suppressed regulatory T cell, M2-like tumor\u2013associated macrophage, and myeloid-derived suppressive cell infiltration. RNA sequencing showed that CCR2\/5i partially inhibited RT-induced TLR2\/4 and RAGE signaling, leading to decreased expression of immunosuppressive cytokines including CCL2\/CCL5, but increased expression of effector T cell chemokines such as CCL17\/CCL22. This study thus supports the clinical development of CCR2\/5i in combination with RT and ICIs for PDAC treatment.<\/jats:p>","DOI":"10.1084\/jem.20211631","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T13:23:18Z","timestamp":1649683398000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["CCR2\/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6583-1281","authenticated-orcid":true,"given":"Jianxin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 1"},{"name":"Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD 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