SLAMF7 Signaling Reprograms T Cells toward Exhaustion in the Tumor Microenvironment

Abstract

P.O. and Y.A.A. conceptualized the study and designed its experiments. P.O., S.H., and Y.A.A. performed all experiments. S.H. and M.K.B. performed IL-2 ELISA experiments. P.O. performed reanalysis of CyTOF data. S.H. performed analysis of TCGA data. S.G. managed all mouse work and genotyped and bred mice. A.A. assisted in experimental design and provided funding. P.O. wrote the manuscript, and all authors assisted in editing the manuscript. Y.A.A. supervised the study. The authorship order of the two cofirst authors was determined based on differing roles in conceptualization of the study and manuscript preparation. P.O. contributed mainly though design, planning, analysis, and writing of the manuscript, while S.H. physically performed many of the experiments and performed data analysis.

Spatiotemporal co-dependency between macrophages and exhausted CD8+T cells in cancer

“…The presence of TAM in solid tumors often correlates with poor prognosis and failure of response to anticancer therapies (Zhang et al, 2012;De Palma and Lewis, 2013). These findings are consistent with the established role of TAM in suppressing anti-tumor T cell immunity (DeNardo and Ruffell, 2019), and recent single cell RNA sequencing studies and other immune profiling approaches have hinted towards a potential link between the presence of TAM and exhausted CD8 + T cells in several different cancer types (Bi et al, 2021;Braun et al, 2021;Combes et al, 2021;Hong et al, 2021;Hu et al, 2020;Mujal et al, 2021;O'Connell et al, 2021;Wagner et al, 2019). However, these computational predictions still require experimental investigation to establish causality.…”

Unique autoantibody prevalence in long-term recovered SARS-CoV-2-infected individuals

“…2 A and B, right), respectively. To assess the post-infectious impact of SARS-CoV-2 on the responsiveness of CD4 + T-cell subpopulations, we conducted analysis of the T-cell surface surrogate markers KLRG1 for terminal differentiation and CTLA-4 for T-cell exhaustion [ 31 ]. In contrast to healthy unexposed donors that showed a correlation between age and CD4 + T-cells expressing KLRG1 (R 2 = 0.10; p = 0.0455, data not shown) no age association of KLRG1 expression could be detected in the convalescents group ( Fig.…”

On the road to eliminating long‐lived plasma cells—“are we there yet?”

“…Like CD38, CS‐1 is expressed at high levels in MM and normal PCs but is also expressed, at lower levels, in other immune cells including NKT cells, T cells, B cells, DCs, and monocytes 124 . Both activating and inhibitory functions have been described and appear to be dependent upon the cell type and may be related to the isoform expressed and presence of signaling adaptor proteins 125‐128 . Interestingly, CS‐1 transcription is regulated by Blimp‐1 and, in B cells, is upregulated upon B‐cell activation 129,130 .…”