التفاصيل البيبلوغرافية
| العنوان: |
LRIG1 engages ligand VISTA and impairs tumor-specific CD8+ T cell responses. |
| المؤلفون: |
Ta, Hieu Minh, Roy, Dia, Zhang, Keman, Alban, Tyler, Juric, Ivan, Dong, Juan, Parthasarathy, Prerana B., Patnaik, Sachin, Delaney, Elizabeth, Gilmour, Cassandra, Zakeri, Amin, Shukla, Nidhi, Rupani, Amit, Phoon, Yee Peng, Liu, Caini, Avril, Stefanie, Gastman, Brian, Chan, Timothy, Wang, Li Lily |
| المصدر: |
Science Immunology; 2024, Vol. 9 Issue 95, p1-17, 17p |
| مصطلحات موضوعية: |
REGULATORY T cells, T cells, CYTOTOXIC T cells, T cell receptors, IMMUNE response, IMMUNE checkpoint proteins, LEUCINE |
| مستخلص: |
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+ CD62Lhi PD-1low) 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. Editor's summary: The negative checkpoint regulator VISTA has emerged as a promising target for cancer immunotherapy. VISTA plays an important role in maintaining T cell quiescence; however, the molecular mechanisms through which VISTA regulates antitumor immunity are not well defined. In this study, Ta et al. identified LRIG1 as a VISTA-binding partner and co-inhibitory receptor. VISTA engagement by LRIG1 impaired murine antitumor immunity by promoting quiescence in tumor-specific CD8 T cells and limited the abundance of progenitor and memory-like cells with the ability to differentiate into effector T cells. In patients with melanoma, expression of LRIG1 on tumor-infiltrating lymphocytes correlated with resistance to immunotherapy. Together, these findings suggest that selectively inhibiting VISTA/LRIG1 may be an effective cancer immunotherapy. —Hannah Isles [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
