Article ; Online: From patient tissue correlates to molecular mechanisms of cancer immune evasion: the emerging role of CD58 and PD-L1 co-regulation via CMTM6.
2023 Volume 25, Issue 1, Page(s) 82–84
Abstract: Immune evasion is a hallmark of cancer, yet the underlying mechanisms are often unknown in many patients. Using single-cell transcriptomics analysis, we previously identified the co-stimulator CD58 as part of a cancer cell-intrinsic immune checkpoint ... ...
| Abstract | Immune evasion is a hallmark of cancer, yet the underlying mechanisms are often unknown in many patients. Using single-cell transcriptomics analysis, we previously identified the co-stimulator CD58 as part of a cancer cell-intrinsic immune checkpoint resistance signature in patient melanoma tissue. We subsequently validated CD58 loss as a driver of immune evasion using a patient-derived co-culture model of cancer and cytotoxic tumor-infiltrating lymphocytes in a pooled single-cell perturbation experiment, where we additionally observed concurrent upregulation of PD-L1 protein expression in melanoma cells with CD58 loss. In our most recent study, we uncovered the mechanisms of immune evasion mediated by CD58 loss, including impaired T cell activation and infiltration within tumors, as well as inhibitory signaling by PD-L1 via a shared regulator, CMTM6. Thus, cancer cell-intrinsic reduction of CD58 represents a multi-faceted determinant of immune evasion. Furthermore, its reciprocal interaction with PD-L1 via CMTM6 provides critical insights into how co-inhibitory and co-stimulatory immune cues are regulated. |
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| MeSH term(s) | Humans ; B7-H1 Antigen/genetics ; Melanoma/genetics ; Immune Evasion ; Cell Line, Tumor ; Signal Transduction |
| Chemical Substances | B7-H1 Antigen |
| Language | English |
| Publishing date | 2023-12-11 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2060566-3 |
| ISSN | 1476-5470 ; 1466-4879 |
| ISSN (online) | 1476-5470 |
| ISSN | 1466-4879 |
| DOI | 10.1038/s41435-023-00224-9 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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