{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:11:19Z","timestamp":1789193479886,"version":"build-2803163510"},"reference-count":38,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Major project of joint medical research of science and health in Chongqing","award":["2025DBXM006"],"award-info":[{"award-number":["2025DBXM006"]}]},{"name":"Funding for Chongqing Young and Middle-Aged Medical Excellence Team","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Middle-aged and Young Medical Talent Project of Chongqing","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"Chongqing Natural Science Foundation Innovation and Development Joint Fund Project","award":["CSTB2025NSCQ-LZX0004"],"award-info":[{"award-number":["CSTB2025NSCQ-LZX0004"]}]},{"name":"National Outstanding Youth Reserve Talent Training Project","award":["HBRC202406"],"award-info":[{"award-number":["HBRC202406"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271885, 82572105 and 32470971"],"award-info":[{"award-number":["82271885, 82572105 and 32470971"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["2024NSCQ-KJFZMSX0059"],"award-info":[{"award-number":["2024NSCQ-KJFZMSX0059"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,1]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have been proven to be one of the most promising and effective immunotherapies; however, their efficacy in colorectal cancer (CRC) remains significantly limited. Therefore, understanding the mechanism of resistance to ICIs therapy in CRC patients is of great significance for the development of new anti-tumor immunotherapy targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ccl7 myeloid cell-specific knockout mice and MC38 tumor-bearing mouse models were established to investigate the role of Ccl7 during CRC progression. Proteomic analysis, RNA-seq, and flow cytometry analysis were used to determine the role of Ccl7 in the tumor immune microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Herein, we found that elevated CCL7\n                      <jats:sup>+<\/jats:sup>\n                      tumor-associated macrophages (TAMs) in tumors correlated with tolerance to ICIs blockage therapy in patients with CRC. Deletion of CCL7 in myeloid cells resulted in reduced accumulation of immunosuppressive TAMs and increased infiltration of activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells within the tumor. Mechanistically, CCL7 modulates peroxisome biogenesis and fatty acid oxidation, thereby promoting the immunosuppressive functions of TAMs via the PI3K-AKT-PEX3 signaling pathway. Furthermore, CCL7 inhibits the expression of chemokine CXCL10 by suppressing the AKT2-STAT1 signaling pathway, which reduces the infiltration of activated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in the tumor. Blocking CCL7 delays CRC progression and enhances the therapeutic efficacy of PD-L1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study highlights the novel role and regulatory mechanisms of CCL7\n                      <jats:sup>+<\/jats:sup>\n                      TAMs in ICIs immunotherapy resistance, suggesting that CCL7 may serve as a potential combined therapeutic target for ICIs immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013027","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T07:00:41Z","timestamp":1764054041000},"page":"e013027","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Macrophage CCL7 promotes resistance to immunotherapy for colorectal cancer by regulating the infiltration of macrophages and CD8\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1136","volume":"13","author":[{"given":"Yijiao","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, People's Republic of China"},{"name":"Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, People's Republic of China"},{"name":"Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiongming","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Kuang","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, People's Republic of China"},{"name":"Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, People's Republic of 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