RNA binding protein PCBP1 is an intracellular immune checkpoint for shaping T cell responses in cancer immunity.
Ephraim A Ansa-AddoHuai-Cheng HuangBrian RiesenbergSupinya IamsawatDavis M BoruckiMichelle H NelsonJin Hyun NamDongjun ChungChrystal M PaulosBei LiuXue-Zhong YuCaroline PhilpottPhilip H HoweZihai LiPublished in: Science advances (2020)
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 (Teff) cells into regulatory T (Treg) cells, by restricting the expression of Teff cell-intrinsic Treg commitment programs. This was critical for stabilizing Teff cell functions and subverting immune-suppressive signals. T cell-specific deletion of Pcbp1 favored Treg 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 Teff cell functions in cancer immunity.
Keyphrases
- binding protein
- single cell
- induced apoptosis
- cell therapy
- papillary thyroid
- cell cycle arrest
- poor prognosis
- reactive oxygen species
- stem cells
- transcription factor
- squamous cell
- squamous cell carcinoma
- public health
- oxidative stress
- cell death
- dendritic cells
- mesenchymal stem cells
- immune response
- endoplasmic reticulum stress
- risk assessment
- signaling pathway
- cell proliferation
- lymph node metastasis
- pi k akt
- human health