{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T07:05:21Z","timestamp":1779433521690,"version":"3.53.1"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"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                    Immunosuppression within the tumor microenvironment (TME) remains a major barrier to durable responses to cancer immunotherapy. CKLF-like MARVEL transmembrane domain-containing 4 (\n                    <jats:italic>CMTM4<\/jats:italic>\n                    ), a member of the CMTM family, has emerged as a regulator of tumor immune regulation and membrane protein trafficking. This critical narrative review summarizes the genetic and structural features of\n                    <jats:italic>CMTM4<\/jats:italic>\n                    , its immunological functions under physiological and pathological conditions, and its multifaceted roles within the immune compartment of the TME. The review focuses on three aspects (1): mechanisms by which\n                    <jats:italic>CMTM4<\/jats:italic>\n                    contributes to programmed death-ligand 1 (PD-L1) stability and interacts with TME-associated membrane proteins (2); cell-type-specific interactions between\n                    <jats:italic>CMTM4<\/jats:italic>\n                    and immune effector or suppressor cells; and (3) its potential value as a candidate prognostic biomarker and therapeutic target for modulating resistance to immune checkpoint inhibitors (ICIs). This review also discusses unresolved mechanistic questions, limitations of current research models, and challenges in clinical translation. Future studies integrating single-cell multi-omics, spatial transcriptomics, proteomics, and organoid models may help clarify the context-dependent functions of\n                    <jats:italic>CMTM4<\/jats:italic>\n                    and provide a stronger basis for its translational evaluation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1741477","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T06:11:35Z","timestamp":1779430295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Research progress of CMTM4 in the tumor immune microenvironment and immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyao","family":"Zhang","sequence":"first","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Tongliao People\u2019s Hospital","place":["Tongliao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qijiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Medical University Affiliated Cancer Hospital","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Medical University Affiliated Cancer Hospital","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cao","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University","place":["Hohhot, China"]},{"name":"Inner Mongolia Medical University Affiliated Cancer Hospital","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University Affiliated Cancer Hospital","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Ji","sequence":"additional","affiliation":[{"name":"Inner Mongolia Medical University Affiliated Cancer Hospital","place":["Hohhot, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.740822","article-title":"CMTM family genes affect prognosis 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