Journal Article

DKFZ-2023-01194

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity.

Ho, P. ; Melms, J. C. ; Rogava, M. ; Frangieh, C. J. ; Poźniak, J. ; Shah, S. B. ; Walsh, Z. ; Kyrysyuk, O. ; Amin, A. D. ; Caprio, L. ; Fullerton, B. T. ; Soni, R. K. ; Ager, C. R. ; Biermann, J. ; Wang, Y. ; Khosravi-Maharlooei, M. ; Zanetti, G. ; Mu, M. ; Fatima, H. ; Moore, E. K. ; Vasan, N. ; Bakhoum, S. F. ; Reiner, S. L. ; Bernatchez, C. ; Sykes, M. ; Mace, E. M. ; Wucherpfennig, K. W. ; Schadendorf, D.DKFZ* ; Bechter, O. ; Shah, P. ; Schwartz, G. K. ; Marine, J.-C. ; Izar, B.

2023
Elsevier New York, NY

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.ccell.2023.05.014

Abstract: 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.

Keyword(s): CD2 ; CD58 ; CRISPR-Cas9 screen ; PDL1 ; balance of co-inhibitory/co-stimulator ; cancer immune evasion ; cancer immunology ; cancer immunotherapy ; immune checkpoint blockade ; mass spec screen ; resistance to immune checkpoint blockade ; single-cell RNA-sequencing

Note: 2023 Jul 10;41(7):1207-1221.e12

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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