Resting Memory Cd4+T Cells And Plasma Cells In Gastric Cancer May Be Potential Immune Biomarkers.

JOURNAL OF CLINICAL ONCOLOGY(2020)

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Abstract
e16523 Background: Previous studies revealed the CD8+T cells deeply involved in tumor progress and reaction to immunotherapy. Now we used expression data and in silicon algorithm to analyze immune cell composition in gastric cancer and explored other subsets of immune cells that may be the potential immune biomarkers. Methods: CIBERSORT quantified 22 immune cell subtypes using four GEO gastric cancer cohorts (GSE15459, GSE26253, GSE29272, GSE57303) and TCGA-STAD, TCGA-PAAD gene expression data, and only CIBERSORT P- value of < 0.05 were included in the survival analysis. Immune cell high was defined as ≥median cells proportion individually and were computed for survival analysis and hazard ratios. Wilcox test was applied to analyze the differences between normal and tumor tissues. Log-rank Mantel-Cox test was applied to compare the survival curves between the patient groups. Statistical analyses were conducted using R v3.3.2. Results: Unsupervised hierarchical analysis of four GEO gastric tumor cohort using 22 immune cells proportions identifies three subclasses. In the subclass with the best overall survival performance, we found enriched resting CD4 T memory cells. Then in TCGA-STAD (P = 0.03) and TCGA-PAAD (P = 0.03) cohort, we observed that normal tissue obtained higher fraction of resting CD4 T memory cells than tumor. On the other hand, in patients who administrated chemotherapy in TCGA-STAD, by comparing immune cell high and low subgroup, we found that plasma cells (P = 0.02), T cells CD8(P = 0.03) were associated with improved overall survival. while, neutrophils(P = 0.05), NK cells resting(P = 0.04), were correlated with decreased overall survival. Also we proved one similar result in GEO cohort, that plasma cells-high (above median) subgroup provided increased overall survival (P = 0.04, HR = 0.76). In contrast, other three immune cells were not significantly associated with survival benefits. Conclusions: Together, these results indicated that memory CD4 T cells and plasma cells infiltration in gastric cancer have important clinical meanings and may be potential immune biomarkers. The continued integration of observations from a variety of experimental models will be required to further understand and utilize the full potential of immune cells.
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Key words
potential immune biomarkers,gastric cancer,memory cd4+,cells
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