Cxcr6-deficiency impairs cancer vaccine efficacy and resident memory CD8+ T-cells recruitment in tumor. - Institut Pasteur Access content directly
Conference Papers Year : 2019

Cxcr6-deficiency impairs cancer vaccine efficacy and resident memory CD8+ T-cells recruitment in tumor.

Abstract

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.
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pasteur-03957364 , version 1 (26-01-2023)

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S Karaki, C Blanc, T Tran, I Galy-Fauroux, M Anson, et al.. Cxcr6-deficiency impairs cancer vaccine efficacy and resident memory CD8+ T-cells recruitment in tumor.. Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, Sep 2018, New York, United States. ⟨10.1158/2326-6074.CRICIMTEATIAACR18-A172⟩. ⟨pasteur-03957364⟩
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