{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:07:47Z","timestamp":1789387667032,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Chemotherapy is one of the important clinical treatments for malignant tumors, but primary or acquired chemotherapy resistance significantly limits patient benefits. Programmed death ligand 1 (PD-L1) has been reported to be regulated by chemotherapy and to contribute to chemotherapy resistance. However, as a novel regulatory molecule of PD-L1, the relationship between CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) and chemotherapy resistance remains understudied. Here, we found that tumor CMTM6 and PD-L1 were upregulated by chemotherapy in clinical cancer patients,\n                    <jats:italic>in vitro<\/jats:italic>\n                    human or mouse tumor models, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    mouse tumor models. PI3K-mTOR was the potential mechanism underlying this effect. CMTM6 deficiency could still reduce chemotherapy-induced tumor PD-L1 expression. And CMTM6 could promote tumor cell resistance to chemotherapy-induced apoptosis and growth arrest, which may be associated with p53.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , both tumor and host CMTM6 and PD-L1 could promote resistance to chemotherapy, and tumor and host CMTM6 knockout could promoted antitumor immune responses during chemotherapy. Moreover, we developed and evaluated the antitumor effects of CMTM6&amp;amp;PD-L1-targeting adeno-associated virus (AAV), which effectively mobilized antitumor immunity and could be combined with chemotherapy. Our findings reveal that both tumor- and host-derived CMTM6 and PD-L1 are regulatory molecules of chemotherapy resistance and can serve as therapeutic targets for combination therapy with chemotherapy.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1886034","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:55:55Z","timestamp":1789386955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CMTM6\/PD-L1-targeted AAV promotes anti-tumor immune responses and chemotherapy responsiveness"],"prefix":"10.3389","volume":"17","author":[{"given":"Runqiu","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiru","family":"Long","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Gong","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Shanghai, China"]},{"name":"Innovation Center for AI and Drug Discovery, School of Pharmacy, East China Normal University","place":["Shanghai, China"]},{"name":"Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences","place":["Zhongshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiqing","family":"Feng","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University","place":["Shanghai, China"]},{"name":"Department of Biological Medicines, School of Pharmaceutical Sciences, Shanghai Engineering Research Center of Immunotherapeutics, Fudan University","place":["Shanghai, 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