{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:40:30Z","timestamp":1793036430898,"version":"4.5.0"},"reference-count":35,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2024-I2M-ZD-001"],"award-info":[{"award-number":["2024-I2M-ZD-001"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902848"],"award-info":[{"award-number":["81902848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971324"],"award-info":[{"award-number":["81971324"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-D-001"],"award-info":[{"award-number":["2022-PUMCH-D-001"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,29]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer-associated fibroblasts (CAFs) are major non-tumor cellular components of the tumor microenvironment (TME) and are closely related to immune suppression. The enhancement of anti-programmed cell death protein-1 (PD-1) efficacy by antiangiogenic tyrosine kinase receptor inhibitors (TKIs) is partly due to the elimination of CAFs, which improves the immunosuppressive microenvironment. However, it remains unclear whether antiangiogenic TKIs regulate the autophagy of CAFs, thereby affecting the immunotherapy response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We first examined the effects of autophagy inhibition and anlotinib on the TME and immunotherapy response via animal experiments. Then, CAF models were established in vitro. The effects and mechanisms of autophagy inhibition on the efficacy of anlotinib and CAFs were further explored in vitro. To specifically validate the role of CAF autophagy, we additionally constructed LLC tumor-bearing mouse models co-implanted with CAFs transfected with ATG5-targeting siRNA or non-targeting control siRNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In anti-PD-1-resistant (LLC) and CAF-rich (LA795+MSC) non-small cell lung cancer models, the autophagy inhibitor chloroquine significantly enhanced anlotinib+anti-PD-1 efficacy\u2014likely by inducing more apoptosis of CAFs and M2 macrophages, reshaping the TME to promote CD8+T\u2009cell infiltration. After ATG5 knockdown (autophagy inhibition) in CAFs, the efficacy-enhancing effect of anti-PD-1 therapy was significantly attenuated versus control, confirming CAF autophagy is core to TME regulation. In vitro, anlotinib induced CAF autophagy via AKT\/mTOR inhibition; inhibiting CAF autophagy enhanced anlotinib-induced CAF apoptosis and impaired CAFs\u2019 ability to recruit M2 macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Autophagy inhibition enhances the effects of antiangiogenic TKIs on tumor cells and CAFs and directly or indirectly regulates the TME, which might explain why autophagy inhibition enhances the efficacy of antiangiogenic TKIs combined with anti-PD-1 therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-010812","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T04:55:15Z","timestamp":1758516915000},"page":"e010812","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Autophagy inhibition improves the efficacy of 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Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-4643","authenticated-orcid":false,"given":"Yingyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 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