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Unidentified

ABSTRACT: Lrig1 marks a novel renal quiescent 1 stem cell population that maintains and repairs 2 proximal tubules (KAP220138)

PROVIDER: PRJDB19256 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	DRR670361_1.fastq.gz	Fastqsanger.gz
	DRR670361_2.fastq.gz	Fastqsanger.gz
	DRR670362_1.fastq.gz	Fastqsanger.gz
	DRR670362_2.fastq.gz	Fastqsanger.gz
	DRR670363_1.fastq.gz	Fastqsanger.gz

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Project description:Cancer immunotherapies boost antitumor immunity and improve the survival of cancer patients. V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an immune 20 checkpoint target but presents elusive signaling mechanisms. We report a novel VISTA binding partner, Leucine-Rich Repeats and Immunoglobulin Like Domains 1 (LRIG1), which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell-specific LRIG1 deletion developed superior antitumor T cell responses. Mechanistically, LRIG1-deficient tumor-specific CD8+ cytotoxic T cells (CTLs) exhibited longer 25 persistence due to improved expansion and survival and greater effector function. Sustained tumor control was also associated with a reduction of quiescent CTLs (TCF1+ CD62Lhi PD-1low) and a reciprocal increase in progenitor and memory-like CTLs (TCF1+ PD-1+). In human melanoma, an elevated LRIG1 expression on tumor-infiltrating CD8+ CTLs correlated with resistance to immunotherapies. Taken together, these results delineate the role of LRIG1 as an inhibitory 30 immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.

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