PDCD1LG2 gene

The PDCD1LG2 gene (PDCD1LG2 is the acronym for Programmed Cell Death 1 Ligand 2) is a protein-coding gene located on chromosome 9p24.1 and an important paralog of this gene is CD274 (alias PD-L1). CD273 is, among other things, a biomarker for pulmonary tuberculosis.

The encoded protein PD-1 ligand 2, aka CD273, is involved in the negative regulation of proliferation of activated T cells, the negative regulation of interleukin-10 production and the negative regulation of type II interferon production. It is assumed that the protein is located in the plasma membrane and is active on the outside of the plasma membrane.
Furthermore, the protein is involved in costimulatory signaling that is essential for T cell proliferation and interferon-gamma production. Interaction with PDCD1 inhibits T cell proliferation by blocking cell cycle progression and cytokine production

Immune checkpoints have been shown to be involved in the activation of the apoptosis pathway in patients with heptatocellular carcinoma (HCC). Expression of the immune checkpoint ligand CD274 (programmed cell death 1 ligand 1, PD-L1, from the CD274 gene) contributes to the suppression of the T cell-mediated antitumor immune response (Masugi Y et al. 2017a).

Thus, PDCD1LG2 expression in tumor is not associated with peritumoral lymphocytic response or survival of patients with HCC. Tumor PDCD1LG2 expression is inversely associated with a Crohn's-like lymphoid response to colorectal cancer, suggesting a possible role of PDCD1LG2-expressing tumor cells in inhibiting the development of tertiary lymphoid tissue during colorectal carcinogenesis (Masugi Y et al. 2017).

Increased expression of PDCD1 and PDCD1LG2 was shown to have a favorable impact on recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS). Positive correlations between PDCD1 and PDCD1LG2 expression and immune biomarkers, immune cells, chemokine receptors and chemokines have been demonstrated. This indicates that PDCD1 and PDCD1LG2 are prognostic biomarkers in HCC and are related to immune infiltration (Li W et al. 2022).

Diseases associated with PDCD1LG2 include hematologic neoplasms (e.g. acute lymphoblastic leukemia) and gastrointestinal malignancies (e.g. HCC). Associated signaling pathways include the phosphorylation of CD3 and TCR zeta chains and the innate immune system.

1. Li W et al. (2022) Identification of PDCD1 and PDCD1LG2 as Prognostic Biomarkers and Associated with Immune Infiltration in Hepatocellular Carcinoma. Int J Gen Med 15:437-449.
2. Masugi Y et al. (2017) Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer. Cancer Immunol Res 5:1046-1055.
3. Masugi Y et al. (2017a) Tumor CD274 (PD-L1) expression and T cells in colorectal cancer. Gut 66:1463-1473.