Distribution characteristics and clinical significance of peripheral blood stem cell-like memory T cells in patients with gastric cancer / 中华微生物学和免疫学杂志

Objective To study the distribution characteristics of peripheral blood stem cell-like memory T cells ( TSCM) in patients with gastric cancer and to analyze their relationship to clinicopathologi-cal characteristics and clinical application value. Methods Thirty-two patients hospitalized with gastric cancer in our hospital from July to December, 2018 were selected as the case group. Twenty-three healthy volunteers recruited during the same period served as the control group. The percentages of TSCM, naive T cells ( TN) and memory T cells ( TM) were detected by flow cytometry and the differences between the two groups were compared. The relationship of clinicopathological features to TN, TSCM, TSCM/TN ratio and TM was analyzed. Results The percentages of TN and TSCM in peripheral blood of the patients were signif-icantly lower than those of the healthy control group, while the ratio of TSCM to TN was significantly in-creased in the case group (all P<0. 05). The proportion of TN was negatively correlated with tumor TNM stage and invasion depth, and positively correlated with the degree of tissue differentiation. The ratio of TSCM to TN was positively correlated with TNM stage, invasion depth and lymph node metastasis. Conclu-sions TN and the ratio of TSCM to TN in peripheral blood of patients with gastric cancer are closely related to clinical and pathological characteristics such as tumor stage and invasion depth, which could be used as a new way to evaluate the immune status of patients. TSCM might have important clinical application value in adoptive cellular immunotherapy of gastric cancer, but large-scale multi-center clinical studies are needed for further evaluation.

Relationship between Poor Immunogenicity of HLA-A2-Restricted Peptide Epitopes and Paucity of Naive CD8+ T-Cell Precursors in HLA-A2-Transgenic Mice

We examined the immunogenicity of H-2 class I-restricted and HLA-A2-restricted epitopes through peptide immunization of HLA-A2-transgenic mice that also express mouse H-2 class I molecules. All four of the tested epitopes restricted by H-2 class I robustly elicited T-cell responses, but four of seven epitopes restricted by HLA-A2 did not induce T-cell responses, showing that HLA-A2-restricted peptide epitopes tend to be poorly immunogenic in HLA-A2-transgenic mice. This finding was confirmed in HLA-A2-transgenic mice infected with a recombinant vaccinia virus expressing hepatitis C virus proteins. We examined the precursor frequency of epitope-specific naive CD8+ T cells in HLA-A2-transgenic and conventional C57BL/6 mice and found that the poor immunogenicity of HLA-A2-restricted peptide epitopes is related to the paucity of naive CD8+ T-cell precursors in HLA-A2-transgenic mice. These results provide direction for the improvement of mouse models to study epitope repertoires and the immunodominance of human T-cell responses.