| First Author | Ta HM | Year | 2024 |
| Journal | Sci Immunol | Volume | 9 |
| Issue | 95 | Pages | eadi7418 |
| PubMed ID | 38758807 | Mgi Jnum | J:350541 |
| Mgi Id | MGI:7663043 | Doi | 10.1126/sciimmunol.adi7418 |
| Citation | Ta HM, et al. (2024) LRIG1 engages ligand VISTA and impairs tumor-specific CD8(+) T cell responses. Sci Immunol 9(95):eadi7418 |
| abstractText | Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, 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 responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1(+) CD62L(hi) PD-1(low)) and a reciprocal increase in progenitor and memory-like CTLs (TCF1(+) PD-1(+)). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8(+) CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy. |
