Pdcd1lg2, also known as PD-L2 or CD273, encodes a ligand for the programmed death receptor 1 (PD-1). Engagement of PD-1 by PD-L2 inhibits T cell receptor-mediated proliferation and cytokine production by CD4+ T cells, leading to cell cycle arrest in G0/G1. This interaction is part of the immune checkpoint pathway, which is crucial in regulating T cell responses and maintaining immune tolerance [4].

In colorectal cancer, tumor Pdcd1lg2 expression was inversely associated with Crohn-like lymphoid reaction, suggesting its role in inhibiting the development of tertiary lymphoid tissues during carcinogenesis [1]. In hepatocellular carcinoma, elevated expression of Pdcd1lg2 was associated with favorable recurrence-free survival, progression-free survival, disease-specific survival, and overall survival, and it was also correlated with immune infiltration [2]. Across multiple cancer types, Pdcd1lg2 expression levels varied, impacted patient prognosis, was associated with clinical characteristics, immune cell types, immunosuppressive biomarkers, and biological pathways related to cancer immunity and metastasis [3]. In malignant pleural mesothelioma, immunohistochemical expression of Pdcd1lg2 was associated with better prognosis [5].

In conclusion, Pdcd1lg2 plays a significant role in the immune checkpoint pathway, regulating T cell responses. Its dysregulation is associated with various cancers, influencing tumor-immune interactions and patient prognosis. Studies on Pdcd1lg2 contribute to a better understanding of cancer immunology and may offer potential biomarkers and therapeutic targets for cancer treatment.

References:

1. Masugi, Yohei, Nishihara, Reiko, Hamada, Tsuyoshi, Nowak, Jonathan A, Ogino, Shuji. 2017. Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer. In Cancer immunology research, 5, 1046-1055. doi:10.1158/2326-6066.CIR-17-0122. https://pubmed.ncbi.nlm.nih.gov/29038297/

2. Li, Wang, Mei, Mei, Liu, Tian, Zhang, NingNing, Lu, Wei. 2022. Identification of PDCD1 and PDCD1LG2 as Prognostic Biomarkers and Associated with Immune Infiltration in Hepatocellular Carcinoma. In International journal of general medicine, 15, 437-449. doi:10.2147/IJGM.S347163. https://pubmed.ncbi.nlm.nih.gov/35046705/

3. Zhou, Xuan, Wang, Yu, Zheng, Jianwei, Ren, Yu, Wang, Xudong. 2022. Integrative study reveals the prognostic and immunotherapeutic value of CD274 and PDCD1LG2 in pan-cancer. In Frontiers in genetics, 13, 990301. doi:10.3389/fgene.2022.990301. https://pubmed.ncbi.nlm.nih.gov/36276934/

4. Latchman, Y, Wood, C R, Chernova, T, Sharpe, A H, Freeman, G J. . PD-L2 is a second ligand for PD-1 and inhibits T cell activation. In Nature immunology, 2, 261-8. doi:. https://pubmed.ncbi.nlm.nih.gov/11224527/

5. Sule Kutlar Dursun, Fatma, Alabalik, Ulas. . Investigation of pd-l1 (cd274), pd-l2 (pdcd1lg2), and ctla-4 expressions in malignant pleural mesothelioma by immunohistochemistry and real-time polymerase chain reaction methods. In Polish journal of pathology : official journal of the Polish Society of Pathologists, 73, 111-119. doi:10.5114/pjp.2022.119752. https://pubmed.ncbi.nlm.nih.gov/36172747/