{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:15:52Z","timestamp":1783595752045,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Guangdong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2025A1515011628"],"award-info":[{"award-number":["2025A1515011628"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>CD8+ T-cell exhaustion is a key mechanism of tumor immune evasion and a major limitation of current cancer immunotherapy. However, the molecular factors sustaining dysfunctional CD8+ T-cell states across cancers are not fully understood. Here, we identify GPR171 as a common feature of exhausted CD8+ T cells across multiple solid tumors based on integrated pan-cancer single-cell transcriptomic analyses. GPR171 is enriched in exhausted CD8+ T cells and is closely associated with immunosuppressive and exhaustion-related gene programs. It also shows a strong association with key immune regulatory genes such as CTLA4 and NR4A2. Functional analyses suggest that reduced GPR171 activity is associated with decreased expression of exhaustion-related genes and a shift toward cytotoxic and immune-activating programs. In parallel, a CREM-centered regulatory network emerges in exhausted CD8+ T cells and may act in concert with GPR171-associated programs to reinforce dysfunctional states. Overall, our results identify GPR171 as a candidate marker of CD8+ T-cell dysfunction across cancers and provide a systematic pan-cancer single-cell characterization of its association with immunosuppressive T-cell states, supporting its potential as a therapeutic target for restoring antitumor immunity.<\/jats:p>","DOI":"10.3390\/ijms27135958","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:25Z","timestamp":1783003885000},"page":"5958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-Cell Pan-Cancer Atlas Reveals GPR171 as a Candidate Marker of CD8+ T-Cell Dysfunction"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4527-5142","authenticated-orcid":false,"given":"Xinyu","family":"Pan","sequence":"first","affiliation":[{"name":"Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guan, Q., Han, M., Guo, Q., Yan, F., Wang, M., Ning, Q., and Xi, D. 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