The assessment of human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) and programmed cell death-ligand 1 (PD-L1) expression is relevant for the selection and effectiveness of targeted therapy in gastric cancer (GC).
We aimed to determine somatic mutational profiles of stage II/III gastric cancers (GCs) according to their tumor microenvironment immune types (TMITs), which classify cancer based on co-assessment of PD-L1 expression and CD8<sup>+</sup> tumor infiltrating lymphocytes.
Immunohistochemistry was performed to detect HLA A/B/C, β2M, CD8, p53, and programmed death-ligand 1 (PD-L1) in the center and invasive margin of the tumor in 395 stage II and III GCs using tissue array method.
Subgroup analysis based on cancer type suggested that PD-L1rs4143815 C > G might increase the susceptibility to gastric cancer (G vs. C: OR = 1.842, 95% CI: 1.403-2.418, p < 0.001) and bladder cancer (G vs. C: OR = 2.015, 95% CI: 1.556-2.608, p < 0.001), and genotype GG carriers of PD-L1rs4143815 C > G might have higher risks of HCC (GG vs. CG + CC: OR = 2.226 95% CI: 1.562-3.172, p < 0.001).
Pembrolizumab was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx test (Dako, Agilent, Santa Clara, CA) for selection of patients with gastric cancer for treatment with pembrolizumab based on PD-L1 tumor expression.
In summary, we identified mutations associated with elevated PD-L1 expression that facilitate the development of better prognostic biomarkers for GC, and might offer insight into the underlying tumor biology.
We aimed to evaluate the expression rates of PD-L1 in GC, and further assess its relationship with mismatch repair (MMR), and human epidermal growth factor receptor 2 (HER2) status.
Our data indicated that blocking IL-8 derived from GCMSCs may overcome the immune escape induced by PD-L1 in GC cells and provide a potential strategy to enhance the immunotherapy efficiency in GC.
We compared IHC staining of PD-L1 in gastric cancer (GC) by using three commercially available antibody clones, and analyzed the correlation with the prognosis.
RNA-seq data from The Cancer Genome Atlas revealed that expression of B7-H1, HDAC1-3, 6-8, and 10 and SIRT1, 3, 5, and 6 was higher, and expression of HDAC5 and SIRT4 was lower in GC compared to that in normal gastric tissues; that HDAC3 and HDAC1 expression level significantly correlated with B7-H1 in GC with a respective r value of 0.42 (p < 0.001) and 0.21 (p < 0.001).