Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients

Abstract

Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis. Correlation with clinical features and outcome were analyzed after controlling for potential confounders including EBV infection, HER2, C-met and PCNA expression. 37.8% of the cases showed membranous PD-L1 expression in tumor cells and 74.9% in infiltrating immune cells. PDL1 expression rate was rather higher in patients without metastasis, in EBV positive group and those with C-met and PCNA expression. GC patients with high level PDL1 expression exhibited better survival. GC Patients with higher T cell infiltration also showed elevated PDL1, PDL2 and PD1 expression and predict favorable outcome, indicating an adaptive immune resistance mechanism may exist. The group of patients infiltrated with lower density CD3+ T cells also without PDL1 expression in tumor cells predict the worst outcome in the subgroup of different PTNM stage, which may suggest an inactive immune status. These results highlights the need to assess both PDL1 expression in all tumor context and the characterization of the GC immune microenvironment.

Programmed death‐ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2‐negative status

“…However, the relationship between PD-L1 expression and the prognosis remains controversial in GC. Many researches showed that PD-L1 expression had a negative impact on patient survival [24][25][26][27], but some studies indicated that PD-L1 positivity was associated with favorable outcomes [16,28]. In our study, PD-L1 expression in GC was related to some adverse clinicopathological characteristics, which was observed more frequently in advanced GCs occurred in the older patients and with bigger tumor size.…”

“…In our study, the positive expression of PD‐L1 was observed in 37.3% cases. PD‐L1 was detected in 15% to 75% of GC patients according to previous literatures . We suppose varied antibodies, different tissue handling methods, and evaluating systems used to define PD‐L1 positivity may all lead to such a wide range of distinct expression rates.…”

Prognostic impact of gene copy number instability and tumor mutation burden in patients with resectable gastric cancer

“…All patients had undergone adjuvant chemotherapy with capecitabine plus oxaliplatin (XELOX). The median number of chemotherapy cycles was 6 (range, [3][4][5][6][7][8][9][10][11][12]. Overall survival (OS) was defined as the time from surgery to death or the last follow-up.…”

Identification of key genes related to dexamethasone-resistance in acute lymphoblastic leukemia

“…CCNB1 and CDK1 have been found to regulated drug sensitiveness not only through cell cycle pathway, but p53 pathway according to our analysis. Previous study also found that PCNA was associated with cancers development [22,23] and patients prognosis [24,25] .…”