High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation

Abstract

The immunohistochemical analysis was used to evaluate the expression of PD-L1 in 109 non-small cell lung cancer (NSCLC) tissues and para-tumor tissues. Associations between expressed PD-L1 and tumor histological types, degree of differentiation, and lymph node metastasis were calculated, and overall survival was assessed. Meanwhile, immunohistochemistry and immunofluorescence double labeling technique were performed to detect the expressions of PD-L1, CD1α, and CD83 on TIDC of 20 lung cancer tissues, and the expression of PD-L1 in CD1α+DCs and CD83+DCs and their significances were also explored. We found that the expression rate of PD-L1 in NSCLC was associated with histological types and overall survival. Patients with either adenocarcinoma or survival time after surgery less than 3 years showed higher expression rate of PD-L1. Furthermore, Cox model analysis indicated that PD-L1 might be regarded as a poor prognostic factor. PD-L1 could be also detected in CD1α+ immature DC in NSCLC, indicating that as a class of key anti-tumor immunocyte in tumor microenvironment, DC expressing PD-L1 itself might play an important role in keeping its immature status and contributing to tumor cells immune escape and disease progression.

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

“…25,[40][41][42] PD-1 and PD-L1 blockade has shown to prolong survival in patients with advanced lung cancer, 17,18,43 indicating that activation of the PD-1/ PD-L pathway inhibits tumor surveillance, thus implicating this pathway as an adverse prognostic factor. However, a recent study demonstrated that PD-L1 (CD274) expression at the protein and mRNA levels was associated with better clinical outcomes in patients with non-small-cell lung cancer.…”

“…Consistent with our results, several reports claimed that elevated PD-L1 expression was predictive of poor clinical outcomes in several cancers including non-small-cell lung cancer. 41,42 Furthermore, upon interaction with PD-1, PD-L1 contributed to an anti-apoptotic effect in tumor cells in a cytosolic domain-dependent manner, 44 indicating that PD-L1 expression in tumor cells might not only induce T-cell exhaustion but also inhibit tumor cell death. In our study, although increased number of CD8 + or PD-1 + tumor-infiltrating lymphocytes were associated with prolonged disease-free survival, a high ratio of PD-1 + /CD8 + tumor-infiltrating lymphocytes was associated with shorter diseasefree survival.…”

Anti-programmed death ligand 1 (PD-L1) inhibitors in metastatic gastric cancer

“…The high PD-L1 expression has been identified as a negative prognostic marker in melanoma [24], RCC [25], and lung cancer [26]. Additionally, PD-L1 upregulation has been detected in gastrointestinal malignancies, such as pancreatic, colorectal, and GC, correlating with poor prognosis [27,28].…”

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

“…Among some of the mechanisms already described to be involved in this scenario, there are known regulatory pathways, such as CTLA-4 and PD-1/PD-L1 pathways, the major negative coreceptor expressed on T-cells [160]. While PD-1-related mechanisms act mainly at later stages, CTLA-4 regulates Tcells activity in earlier stages of tumor growth.…”