Plays a critical role in induction and maintenance of immune tolerance to self ( ). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response ( ). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) . Can also act as a transcription coactivator: in response to hypoxia, translocates into the nucleus via its interaction with phosphorylated STAT3 and promotes transcription of GSDMC, leading to pyroptosis .
The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (, ). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity).
Subcellular locations: Cell membrane, Early endosome membrane, Recycling endosome membrane, Nucleus
Associates with CMTM6 at recycling endosomes, where it is protected from being targeted for lysosomal degradation . Translocates to the nucleus in response to hypoxia via its interaction with phosphorylated STAT3 .
Subcellular locations: Cell membrane
Subcellular locations: Endomembrane system
Subcellular locations: Secreted
Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes.
Widely expressed, highest in lung, liver and pituitary and in various peripheral blood cells, including neutrophils and some subtypes of lymphoid and myeloid cells.