Mauro Di Pilato, Ph.D., Principal Investigator, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Department of Immunology, The University of Texas MD Anderson Cancer Center speaks about CXCR6 Positions Cytotoxic T cells To Receive Critical Survival Signals In The Tumor Microenvironment.
Link to Article:
https://www.cell.com/cell/fulltext/S0092-8674(21)00856-4#%20
Emphasizes:
• CXCR6 is required for long-term tumor suppression by CD8+ cytotoxic T cells (CTLs)
• CXCR6 improves CTL interactions with typical DCs in the CCR7+ DC3 state.
• To survive in the TME, DC3s trans-present IL-15 to TCF-1neg effector-like CTLs.
• DC3s are densely clustered in the tumor stroma’s T cell-rich perivascular niches.
Overview:
CTL responses against malignancies are sustained by stem-like memory cells that not only self-renew but also produce effector-like cells. Tumor tolerance develops as the latter lose their anti-tumor action and develop an epigenetically fixed, hypofunctional state. We show that the transformation of stem-like CTLs into effector-like CTLs is accompanied by a significant chemotactic reprogramming that includes the overexpression of the chemokine receptor CXCR6. CCR7+ dendritic cells (DCs) expressing the CXCR6 ligand CXCL16 place effector-like CTLs in a distinct perivascular niche of the tumor stroma, which is densely populated by CCR7+ DCs. The survival cytokine interleukin-15 is also expressed and trans-presented by CCR7+ DCs (IL-15). CXCR6 expression and IL-15 trans-presentation are required for effector-like CTL survival and local proliferation in the tumor microenvironment in order to optimize anti-tumor action before the irreversible malfunction. These findings hint at a cellular and molecular gatekeeper that controls the size and effectiveness of anti-tumor immune responses.