Prognostic relevance of programmed cell death 1 ligand 2 (PDCD1LG2/PD-L2) in patients with advanced stage colon carcinoma treated with chemotherapy.

Abstract

Colorectal cancer (CRC) is the leading cause of cancer-related mortality worldwide. Although the role of tumor programmed cell death 1 ligand 1 (PD-L1) in suppressing antitumor immunity has been validated in various malignances, the impact of PD-L2 (PD-L2/PDCD1LG2) within tumors remains elusive. Here, we examined tumor PD-L2 expression by immunohistochemical analysis and assessed its association with clinicopathological characteristics and the infiltration of intratumoral T lymphocytes in colon carcinoma patients (n = 1264). We found that tumor PD-L2 status was correlated with perineural invasion (PNI) and associated with survival outcome in colon carcinoma patients. The level of tumor PD-L2 was positively associated with tumor PD-L1 expression but inversely associated with the density of CD8+ tumor-infiltrating lymphocytes (TILs). Patients with elevated tumor PD-L2 levels had a favorable 5-year overall survival (OS) compared to patients with low PD-L2 levels (57% vs 40%, p < 0.001), especially in advanced stage colon carcinoma patients. Low tumor PD-L2 expression was associated with an increased 5-year OS risk among advanced stage colon carcinoma patients by univariate analysis [hazard ratio (HR) = 1.69, 95% CI 1.324-2.161, p < 0.001] and multivariate analysis [HR = 1.594, 95% CI 1.206-2.106, p = 0.001]. Moreover, tumor PD-L2 expression was inversely associated with the lymphocytic reaction in advanced stage colon carcinoma, suggesting that PD-L2 may be upregulated by a compensatory mechanism to inhibit T cell-mediated anticancer immunity. Taken together, these results show that tumor PD-L2 expression may be an independent prognostic factor for survival outcome in patients with advanced stage colon carcinoma.

• Authors: Kevin Chih-Yang Huang, Shu-Fen Chiang, Tsung-Wei Chen, William Tzu-Liang Chen, Pei-Chen Yang, Tao-Wei Ke, K S Clifford Chao
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 22330 (12 18 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 33339860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Ligands
• PDCD1LG2 protein, human
• Programmed Cell Death 1 Ligand 2 Protein

Topics

• Adult
• Aged
• Aged, 80 and over
• Apoptosis (genetics)
• Biomarkers, Tumor (genetics)
• CD8-Positive T-Lymphocytes (metabolism, pathology)
• Carcinoma (genetics, pathology)
• Colorectal Neoplasms (genetics, pathology)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Ligands
• Male
• Middle Aged
• Prognosis
• Programmed Cell Death 1 Ligand 2 Protein (genetics)
• Proportional Hazards Models
• T-Lymphocytes (metabolism, pathology)
• Tumor Microenvironment (genetics)