FOXP3+ Tregs exhibit different infiltrating status and predict a distinct prognosis in primary lesions and hepatic metastases in stage III&IV advanced gastric cancer

Abstract

Advanced gastric cancer (AGC) patients with hepatic metastasis have a somber prognosis. Furthermore, understanding the molecular mechanisms and immune cells infiltrating status in the hepatic metastases event in gastric cancer become quite imperative and pressing. In this study, CD3⁺ T lymphocytes, CD8⁺ T lymphocytes and PD-L1 were favorable prognostic indicators. The positive expression of PD-L1 indicates better prognosis, and FOXP3^highPD-L1^neg could be regarded as a poor prognostic factor in the multivariate analysis in primary lesions. The infiltration of FOXP3⁺ Treg is significantly higher in primary tumor lesions than paired hepatic metastatic lesions (P<0.0001). In AGC patients with hepatic metastasis, low infiltration of FOXP3⁺ Tregs both on primary lesions and metastatic lesions indicate better prognosis. Besides, compared with this in hepatic metastases, the proportion of PD-1⁺CD8⁺ T lymphocytes in CD8⁺ T lymphocytes was elevated in the primary lesions. Moreover, compared with Tregs which were infiltrated in primary lesions, they exhibit higher immunosuppressive effects on hepatic metastases despite the decrease in number. Thus, FOXP3⁺ Tregs exhibit different infiltrating status and predict a distinct prognosis in primary lesions and hepatic metastases, impling the immunological heterogeneity of primary and metastatic lesions in AGC. These conclusions would provide further theoretical basis and a potential target for immunotherapy of AGC.

Keywords: FOXP3+ regulatory T cell; Gastric carcinoma; PD-L1; hepatic metastasis; prognosis.