High‐dimensional analyses reveal a distinct role of T‐cell subsets in the immune microenvironment of gastric cancer

Abstract

Objectives. To facilitate disease prognosis and improve precise immunotherapy of gastric cancer (GC) patients, a comprehensive study integrating immune cellular and molecular analyses on tumor tissues and peripheral blood was performed. Methods. The association of GC patients' outcomes and the immune context of their tumors was explored using multiplex immunohistochemistry (mIHC) and transcriptome profiling. Potential immune dysfunction mechanism/s in the tumors on the systemic level was further examined using mass cytometry (CyTOF) in complementary peripheral blood from selected patients. GC cohorts with mIHC and gene expression profiling data were also used as validation cohorts. Results. Increased CD4 + FOXP3 + T-cell density in the GC tumor correlated with prolonged survival. Interestingly, CD4 + FOXP3 + T cells had a close interaction with CD8 + T cells rather than tumor cells. High densities of CD4 + FOXP3 + T cells and CD8 + T cells (High-High) independently predicted prolonged patient survival. Furthermore, the interferon-gamma (IFN-c) gene signature and PDL1 expression were up-regulated in this group. Importantly, a subgroup of genomically stable (GS) tumors and tumors with chromosomal instability (CIN) within this High-High group also had excellent survival. The High-High GS/CIN tumors were coupled with increased frequencies of Tbet + CD4 + T cells and central memory CD4 + T cells in the peripheral blood. Conclusion. These novel findings identify the combination of CD8 + T cells and FOXP3 + CD4 + T cells as a significant prognostic marker for GC

Molecular Subtypes and CD4+ Memory T Cell-Based Signature Associated With Clinical Outcomes in Gastric Cancer

“…However, Wang et al. showed that GC patients with higher levels of CD4+ T cells were associated with a good prognosis ( 50 ), which was consistent with the findings of the current study.…”

“…Shen et al indicated that CD4 + T cells were related with more advanced stages of gastric cancer (48); Kindlund et al also found that CD4 + regulatory T cells can enhance tumor proliferation mediated by IL-10 and TGF-b (49). However, Wang et al showed that GC patients with higher levels of CD4+ T cells were associated with a good prognosis (50), which was consistent with the findings of the current study.…”

Infiltrating Immune Cells in Gastric Cancer: A Novel Predicting Model for Prognosis

“…International Publisher revealed that many solid tumors are associated with immune cell infiltration in the tumor immune microenvironment (TIME) which affects therapy efficacy and overall survival to no small extent [7][8][9]. A study revealed that high T-cell subsets density in gastric cancer was associated with prolonged survival [10]. What is more, it was thought that natural killer cells and dendritic cells were promising targets of immunity therapy for gastric cancer [11,12].…”

Progress and applications of mass cytometry in sketching immune landscapes

“…With relative high cellular throughput and high dimensions, CyTOF is an ideal and potent technique that reveals intratumor heterogeneity in a variety of tumors, including breast, [70][71][72][73] lung, [74][75][76][77] oropharyngeal, 78 brain, [79][80][81][82][83] colon, 7,11,84,85 ovarian, 86,87 kidney, 88,89 gastric cancer, 90,91 leukemia and lymphoma, 19,[92][93][94][95] and melanoma. 96,97 A summary of single-cell CyTOF studies on primary tumors of various human cancers is presented in Table 3.…”