Distribution, phenotype and dysfunctional mechanism of CD8+ CD103+ tissue-resident memory T cells in gastric cancer patients

Abstract

Objective To investigate the distribution and phenotypic features of CD8+CD103+ tissue-resident memory T cells (Trm) in gastric cancer (GC) patients, and to explore their dysfunctional mechanism. Methods The number of CD8+CD103+ Trm cells in GC tissues was detected by immunohistochemical staining and its correlation with clinical stages of GC patients was subsequently analyzed. The proportion, phenotype and function of CD8+CD103+ Trm cells in tissues of GC patients were determined using flow cytometry. In addition, CD8+ T cells were cultured with transforming growth factor-β1(TGF-β1) stimulation in vitro, and the effects of TGF-β1 on the function of CD8+CD103+ Trm cells were explored. Results The number of CD8+CD103+ Trm cells in GC tissues was not greatly altered (P>0.05), but its proportion in CD8+ T cells was significantly declined than that of normal tissues (P < 0.05). The main population of tumor-infiltrating CD8+CD103+ Trm cells belonged to the type of effector memory cells (CD45RA-CCR7-), which showed higher expression of CD69 and PD-1 while lower expression of granzyme B and perforin than CD8+CD103- T cells (P < 0.05). In vitro culture displayed that TGF-β1 induced the down-regulation of granzyme B and perforin expression in CD8+CD103+ Trm cells. Moreover, the number of tumor-infiltrating CD8+CD103+ Trm cells in advanced GC patients was found significantly decreased than that in early GC patients (P < 0.05). Conclusion The infiltration level of CD8+CD103+ Trm cells in GC tissues is negatively correlated with GC progression. These cells show an inhibitory phenotype as well as decreased anti-tumor function, thus contributing to immune escape of GC.

Keywords

• astric cancer
• cd8+cd103+ trm cells
• tgf-β1
• disease progression