Immunization route is directly correlated with cancer vaccine efficacy. Our team previously showed that mucosal (intranasal, i.n.) and systemic (intramuscular) vaccinations are both able to induce systemic specific CD8+ T-cells but only i.n. immunization allows an efficient control of mucosal tumor growth. Indeed, the i.n. vaccination favors the tumor infiltration of specific CD8+ T-cells and especially tissue-resident memory T-cells (Trm), which are crucial for a potent antitumor activity. Based on a transcriptomic analysis, we have identified a chemokine receptor, CXCR6, highly expressed by these specific Trm CD8+ T-cells, induced by the i.n. vaccination. To understand the role of CXCR6 in vaccination efficacy, we have set up a body of experiments using heterozygous Cxcr6gfp/+ mice, where GFP reflects CXCR6 expression and homozygous Cxcr6-deficient mice Cxcr6gfp/gfp.We have then confirmed CXCR6 expression on specific Trm CD8+ T-cells induced by i.n. vaccination in lung mucosa. Using an orthotopic head and neck tumor model, CXCR6 expression on tumor-infiltrating Trm induced by i.n. immunization has also been reported. In addition, we showed that Cxcr6-deficiency impairs mice survival in a prophylactic and therapeutic i.n. vaccination settings in various mucosal tumor models. In this Cxcr6-deficient mouse model, the loss of vaccine-induced protection against tumor graft correlates with a clear reduction of Trm infiltration in tumor. Finally, in a cohort of human lung cancer, we have observed endogenous CXCR6+ Trm infiltrating these tumors in situ. To conclude, we have identified CXCR6 as a required parameter to recruit the crucial anti-tumor Trm in mucosal tumor. Our results finally indicate that CXCR6 might be a new surrogate biomarker to evaluate antitumor vaccine efficacy.
Citation Format: Soumaya Karaki, Charlotte Blanc, Thi Tran, Isabelle Galy-Fauroux, Marie Anson, Rachel Golub, Eric Tartour. Cxcr6-deficiency impairs cancer vaccine efficacy and resident memory CD8+ T-cells recruitment in tumor [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A172.