التفاصيل البيبلوغرافية
| العنوان: |
The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity. |
| المؤلفون: |
Ho, Patricia1,2 (AUTHOR), Melms, Johannes C.1,2 (AUTHOR), Rogava, Meri1,2 (AUTHOR), Frangieh, Chris J.3,4 (AUTHOR), Poźniak, Joanna5,6 (AUTHOR), Shah, Shivem B.1,2 (AUTHOR), Walsh, Zachary1,2 (AUTHOR), Kyrysyuk, Oleksandr7 (AUTHOR), Amin, Amit Dipak1,2 (AUTHOR), Caprio, Lindsay1,2 (AUTHOR), Fullerton, Benjamin T.1 (AUTHOR), Soni, Rajesh Kumar8 (AUTHOR), Ager, Casey R.1,2 (AUTHOR), Biermann, Jana1,2,9 (AUTHOR), Wang, Yiping1,2,9 (AUTHOR), Khosravi-Maharlooei, Mohsen2,10 (AUTHOR), Zanetti, Giorgia2 (AUTHOR), Mu, Michael1,2 (AUTHOR), Fatima, Hijab11 (AUTHOR), Moore, Emily K.2,12 (AUTHOR) |
| المصدر: |
Cancer Cell. Jul2023, Vol. 41 Issue 7, p1207-1207. 1p. |
| مصطلحات موضوعية: |
*PROGRAMMED cell death 1 receptors, *PROGRAMMED death-ligand 1, *IMMUNE checkpoint proteins, *IMMUNITY, *PROTEIN stability, *T cells |
| مستخلص: |
The cell-autonomous balance of immune-inhibitory and -stimulatory signals is a critical process in cancer immune evasion. Using patient-derived co-cultures, humanized mouse models, and single-cell RNA-sequencing of patient melanomas biopsied before and on immune checkpoint blockade, we find that intact cancer cell-intrinsic expression of CD58 and ligation to CD2 is required for anti-tumor immunity and is predictive of treatment response. Defects in this axis promote immune evasion through diminished T cell activation, impaired intratumoral T cell infiltration and proliferation, and concurrently increased PD-L1 protein stabilization. Through CRISPR-Cas9 and proteomics screens, we identify and validate CMTM6 as critical for CD58 stability and upregulation of PD-L1 upon CD58 loss. Competition between CD58 and PD-L1 for CMTM6 binding determines their rate of endosomal recycling over lysosomal degradation. Overall, we describe an underappreciated yet critical axis of cancer immunity and provide a molecular basis for how cancer cells balance immune inhibitory and stimulatory cues. [Display omitted] • Loss of CD58 expression confers immune evasion through multiple mechanisms • CD58 and PD-L1 are co-regulated in cancer cells • Genome-scale screens identify CMTM6 as important regulator of CD58 • CD58 and PD-L1 compete for CMTM6 for protein stability Ho et al. identify a critical role for defects in the CD58-CD2 axis as drivers of immune evasion and impaired intratumoral T cell infiltration. CD58 and PD-L1 compete for CMTM6 for protein stabilization, thus representing an additional mechanism for balancing immune-stimulatory and -inhibitory signals. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
