RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32523987.
- Also identified by DOI 10.1126/sciadv.aaz3865 and PMC identifier 7259945.
- Licence recorded as CC BY-NC.
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Abstract
Distinct lineages of T cells can act in response to various environmental cues to either drive or restrict immune-mediated pathology. Here, we identify the RNA binding protein, poly(C)-binding protein 1 (PCBP1) as an intracellular immune checkpoint that is up-regulated in activated T cells to prevent conversion of effector T (T<sub>eff</sub>) cells into regulatory T (T<sub>reg</sub>) cells, by restricting the expression of T<sub>eff</sub> cell-intrinsic T<sub>reg</sub> commitment programs. This was critical for stabilizing T<sub>eff</sub> cell functions and subverting immune-suppressive signals. T cell-specific deletion of <i>Pcbp1</i> favored T<sub>reg</sub> cell differentiation, enlisted multiple inhibitory immune checkpoint molecules including PD-1, TIGIT, and VISTA on tumor-infiltrating lymphocytes, and blunted antitumor immunity. Our results demonstrate a critical role for PCBP1 as an intracellular immune checkpoint for maintaining T<sub>eff</sub> cell functions in cancer immunity.
Medical subject headings
- Neoplasms
- T-Lymphocytes, Regulatory