期刊
FRONTIERS IN IMMUNOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1022136
关键词
CXCR6; CXCL16; resident memory T cell; dendritic cell; mucosal vaccination; CAR T cell; immunotherapy
类别
资金
- Fondation ARC pour la recherche sur le cancer [SIGN'IT20181007747, PGA12019110000946_1581]
- INCA [2019-1-PLBIO05-1, PLBIO22-147]
- Foncer contre le Cancer
- SIRIC CARPEM
- Labex Immuno-Oncology
- Ligue contre le cancer (MucoRNAVax)
- IDEX Universite de Paris [AMICD27CD70BLOC]
- Inserm Transfert [MAT-PI20278-1]
- Marie SklodowskaCurie Program Training Network for Optimizing Adoptive T Cell Therapy of Cancer - H2020 Program of the European Union [955575]
- Hector Foundation
- International Doctoral Program i-Target: Immunotargeting of Cancer - Elite Network of Bavaria
- Melanoma Research Alliance Grants [409510]
- Else Kroner-Fresenius- Stiftung [2021_ EKFK_ 01]
- German Cancer Aid
- Ernst-Jung-Stiftung
- LMU Munich's Institutional Strategy LMUexcellent
- m4-award of the Bavarian Ministry for economical affairs
- Marie Curie Actions (MSCA) [955575] Funding Source: Marie Curie Actions (MSCA)
CXCR6 is a receptor that interacts with the chemokine CXCL16 and serves as a marker for immunosurveillance and immunotherapy response. It plays a role in controlling tumor proliferation by CD8(+) T cells and NKT cells. Additionally, it is associated with the efficacy of anti-tumor vaccination and intratumoral accumulation of CAR-T cells.
CXCR6 is a receptor for the chemokine CXCL16, which exists as a membrane or soluble form. CXCR6 is a marker for resident memory T (T-RM) cells that plays a role in immunosurveillance through their interaction with epithelial cells. The interaction of CXCR6 with CXCL16 expressed at the membrane of certain subpopulations of intratumor dendritic cells (DC) called DC3, ideally positions these CXCR6(+) T cells to receive a proliferation signal from IL-15 also presented by DC3. Mice deficient in cxcr6 or blocking the interaction of CXCR6 with its ligand, experience a poorer control of tumor proliferation by CD8(+) T cells, but also by NKT cells especially in the liver. Intranasal vaccination induces CXCL16 production in the lungs and is associated with infiltration by T-RM expressing CXCR6, which are then required for the efficacy of anti-tumor vaccination. Therapeutically, the addition of CXCR6 to specific CAR-T cells enhances their intratumoral accumulation and prolongs survival in animal models of pancreatic, ovarian and lung cancer. Finally, CXCR6 is part of immunological signatures that predict response to immunotherapy based on anti-PD-(L)1 in various cancers. In contrast, a protumoral role of CXCR6(+)T cells has also been reported mainly in Non-alcoholic steatohepatitis (NASH) due to a non-antigen specific mechanism. The targeting and amplification of antigen-specific T-RM expressing CXCR6 and its potential use as a biomarker of response to immunotherapy opens new perspectives in cancer treatment.
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