LRIG1 interacts with VISTA and suppresses tumor-specific CD8+ T cell responses. LRIG1 is an inhibitory receptor that binds VISTA, an immune checkpoint protein, and impairs T cell signaling. Mice with T cell-specific LRIG1 deletion showed enhanced antitumor responses due to increased expansion and function of tumor-specific CD8+ T cells. LRIG1 deficiency reduced quiescent CD8+ T cells and increased progenitor and memory-like CD8+ T cells. In melanoma patients, elevated LRIG1 expression on CD8+ T cells correlated with resistance to immunotherapy. These findings suggest that LRIG1 is an inhibitory immune checkpoint receptor and that targeting the VISTA/LRIG1 axis could be a therapeutic strategy for cancer immunotherapy. LRIG1 is expressed on activated CD8+ T cells and is involved in regulating T cell proliferation, survival, and effector function. LRIG1 deficiency increased CD8+ T cell expansion, persistence, and effector function, leading to improved antitumor responses. LRIG1 promotes the quiescence of CD8+ T cells and reduces the abundance of progenitor/memory-like cells. LRIG1 is expressed in human CD8+ TILs and is associated with resistance to cancer immunotherapies. These results highlight the role of LRIG1 as an immune checkpoint receptor and suggest that targeting the VISTA/LRIG1 axis may be a promising approach for cancer immunotherapy.LRIG1 interacts with VISTA and suppresses tumor-specific CD8+ T cell responses. LRIG1 is an inhibitory receptor that binds VISTA, an immune checkpoint protein, and impairs T cell signaling. Mice with T cell-specific LRIG1 deletion showed enhanced antitumor responses due to increased expansion and function of tumor-specific CD8+ T cells. LRIG1 deficiency reduced quiescent CD8+ T cells and increased progenitor and memory-like CD8+ T cells. In melanoma patients, elevated LRIG1 expression on CD8+ T cells correlated with resistance to immunotherapy. These findings suggest that LRIG1 is an inhibitory immune checkpoint receptor and that targeting the VISTA/LRIG1 axis could be a therapeutic strategy for cancer immunotherapy. LRIG1 is expressed on activated CD8+ T cells and is involved in regulating T cell proliferation, survival, and effector function. LRIG1 deficiency increased CD8+ T cell expansion, persistence, and effector function, leading to improved antitumor responses. LRIG1 promotes the quiescence of CD8+ T cells and reduces the abundance of progenitor/memory-like cells. LRIG1 is expressed in human CD8+ TILs and is associated with resistance to cancer immunotherapies. These results highlight the role of LRIG1 as an immune checkpoint receptor and suggest that targeting the VISTA/LRIG1 axis may be a promising approach for cancer immunotherapy.