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There is an urgent medical need to elucidate how cancer cells evade immune response and to develop novel means to boost the efficacy of immune checkpoint inhibitors. In this study, alcohol induces ligand programmed cell death receptor 1 (PD\u2010L1) expression of CRC cells in vitro and in vivo. Alcohol exposure is shown to induce aldehyde dehydrogenase 2 (ALDH2) expression that is a crucial enzyme involved in alcohol metabolism, and low level of lymphocytes infiltration in the murine CRC model and patients. Intriguingly, ALDH2 and PD\u2010L1 protein expression are positively correlated in tumor tissues from the CRC patients. Mechanistically, ALDH2 stabilizes PD\u2010L1 protein expression by physically interacting with the intracellular segment of PD\u2010L1 and inhibiting its proteasome\u2010dependent degradation mediated by an E3 ubiquitin ligase Speckle Type POZ Protein (SPOP). Importantly, inhibition of ALDH2 reduces PD\u2010L1 protein in CRC cells and promotes tumor\u2010infiltrating T cells (TILs) infiltration, presumably leading to the significant potentiation of anti\u2010PD\u20101 antibody efficacy in a mouse CT26 CRC model. The findings highlight a crucial role played by ALDH2 to facilitate alcohol\u2010mediated tumor escape from immunity surveillance and promote tumor progression.<\/jats:p>","DOI":"10.1002\/advs.202003404","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T01:04:20Z","timestamp":1616634260000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Aldehyde Dehydrogenase 2 Mediates Alcohol\u2010Induced Colorectal Cancer Immune Escape through Stabilizing PD\u2010L1 Expression"],"prefix":"10.1002","volume":"8","author":[{"given":"Hong","family":"Zhang","sequence":"first","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Xia","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Luo","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Yang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Liang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sainan","family":"An","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaocong","family":"Wu","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Chen","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xu","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyan","family":"Cai","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Esophageal Cancer Institute  Guangzhou 510060 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth K. 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