CD274

CD is the acronym for the term "Cluster of Differentiation". "CD" refers to groups of cellular surface features that have been classified according to biochemical or functional criteria. The CD classification enables comprehensible transparency in immunohistological and immunological diagnostics. Currently > 400 cluster molecules are defined and assigned. The protein name is not always identical to the gene name (e.g. CD4 clone 1F6; CD8 clone DK25).

The CD molecules are mainly membrane-bound glycoproteins. Some of these are expressed in a cell-specific manner. Their detection can therefore have a high diagnostic value in neoplastic and inflammatory processes. Some of the proteins included in the CD classification have receptor or signaling functions, while others exert enzymatic activities or are part of intercellular communication.

CD 274, also known as PD-L1, plays a crucial role in the induction and maintenance of immune tolerance to self (Freeman GJ et al. (2000). CD 274 is encoded by the PD-L1 gene located on chromosome 9p24.1.

As a ligand for the inhibitory receptor PDCD1/PD-1, it modulates the activation threshold of T cells and limits the T cell effector response (Mezzadra R et al. 2017). Through an as yet unknown activating receptor, it can costimulate T cell subsets that predominantly produce interleukin-10 (IL10) (Dong H et al.1999). May also act as a transcriptional coactivator: in response to hypoxia, it translocates to the nucleus through its interaction with phosphorylated STAT3 and promotes transcription of GSDMC, leading to pyroptosis (Hou J et al.2020).

The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate antitumor immunity and evade destruction by the immune system, thereby facilitating tumor survival. Interaction with PDCD1/PD-1 inhibits the effector function of cytotoxic T lymphocytes (CTLs). Blockade of the PDCD1-mediated pathway leads to reversal of the exhausted T cell phenotype and normalization of the antitumor response, providing a rationale for cancer immunotherapy .

Diseases associated with CD274 include hematologic cancers and acute lymphoblastic leukemia

A number of checkpoint blockade inhibitors have been developed, including pembrolizumab and nivolumab, which target the PD1/PDL1 interaction. This results in T cells being able to recognize tumor cells without being deactivated by the tumor or its cytokine products

1. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9.
2. Freeman GJ et al. (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027-1034.
3. Hou J et al.(2020) PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumor necrosis. Nat Cell Biol 22:1264-1275.
4. Mezzadra R et al. (2017) Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 549: 106-110.