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CD27 stimulation enhances T cell survival and effector functions, thus providing opportunities to develop therapeutic strategies. The current study aims to investigate the role of endogenous CD27 signaling in tumor growth and metastasis. CD8\u2009+\u2009T cell-specific CD27 knockout (CD8Cre-CD27fl) mice were developed, while global CD27 knockout (KO) mice were also used in our studies. Flow cytometry analyses confirmed that CD27 was deleted specifically from CD8\u2009+\u2009T cells without affecting CD4\u2009+\u2009T cells, B cells, and HSPCs in the CD8Cre-CD27fl mice, while CD27 was deleted from all cell types in global CD27 KO mice. Tumor growth and metastasis studies were performed by injecting B16-F10 melanoma cells subcutaneously (right flank) or intravenously into the mice. We have found that global CD27 KO mice succumbed to significantly accelerated tumor growth compared to WT controls. In addition, global CD27 KO mice showed a significantly higher burden of metastatic tumor nests in the lungs compared to WT controls. However, there was no significant difference in tumor growth curves, survival, metastatic tumor nest counts between the CD8Cre-CD27fl mice and WT controls. These results suggest that endogenous CD27 signaling inhibits tumor growth and metastasis via CD8\u2009+\u2009T cell-independent mechanisms in this commonly used melanoma model, presumably through stimulating antitumor activities of other types of immune cells.<\/jats:p>","DOI":"10.1007\/s00262-024-03780-9","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T13:08:23Z","timestamp":1722949703000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CD27 signaling inhibits tumor growth and metastasis via CD8\u2009+\u2009T cell-independent mechanisms in the B16-F10 melanoma model"],"prefix":"10.1007","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-8904","authenticated-orcid":false,"given":"Eswara Rao","family":"Puppala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"3780_CR1","doi-asserted-by":"publisher","first-page":"715909","DOI":"10.3389\/fimmu.2021.715909","volume":"12","author":"F Lutfi","year":"2021","unstructured":"Lutfi F et al (2021) Targeting the CD27-CD70 pathway to improve outcomes in both checkpoint immunotherapy and allogeneic hematopoietic cell transplantation. 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