Immune Profiling in Gastric Cancer Reveals the Dynamic Landscape of Immune Signature Underlying Tumor Progression

The profiling of the tumor immune microenvironment (TIME) is critical for guiding immunotherapy strategies. However, how the composition of the immune landscape affects the tumor progression of gastric cancer (GC) is ill-defined. Here, we used mass cytometry to perform simultaneous in-depth immune profiling of the tumor, adjacent tissues, and blood cells from GC patients and revealed a unique GC tumor-immune signature, where CD8⁺ T cells were present at a lower frequency in tumor tissues compared to adjacent tissues, whereas regulatory T cells and tumor-associated macrophages (TAMs) were significantly increased, indicating strong suppressive TIME in GC. Incorporated with oncogenic genomic traits, we found that the unique immunophenotype was interactively shaped by a specific GC gene signature across tumor progression. Earlier-stage GC lesions with IFN signaling enrichment harbored significantly altered T-cell compartments while advanced GC featured by metabolism signaling activation was accumulated by TAMs. Interestingly, PD-1 expression on CD8⁺ T cells was relatively higher in earlier-stage GC patients, indicating that these patients may derive more benefits from PD-1 inhibitors. The dynamic properties of diverse immune cell types revealed by our study provide new dimensions to the immune landscape of GC and facilitate the development of novel immunotherapy strategies for GC patients.