Impact of neoadjuvant chemotherapy on lymphocytes and co-inhibitory B7-H4 molecule in gastric cancer: low B7-H4 expression associates with favorable prognosis

Abstract

Little is known on the immune response after neoadjuvant chemotherapy (NACT) in gastric cancer (GC). The present study aimed to investigate the effects of NACT on tumor cells and tumor-infiltrating lymphocytes (TILs) in patients with GC. Expressions of CD4+ and CD8+ TILs and identified co-inhibitory B7-H4 molecule were examined by immunohistochemical staining in GC tissues of 56 patients who received NACT (NACT group) and 46 patients who did not receive NACT (nNACT group). These markers, clinicopathological features, and overall survival (OS) time between both groups were compared. Results showed that the clinicopathological features of patients were not significantly associated with NACT (P > 0.05), but the rate of low expression of B7-H4 (78.6 vs. 47.8 %, P = 0.005) and rate of high expression of CD4+ TILs (58.9 vs. 39.1 %, P = 0.048) and CD8+ TILs (92.9 vs. 56.5 %, P < 0.001) were both significantly higher in NACT group than that in nNACT group. Further, Kaplan-Meier analysis indicated that there was no significant difference in OS time between the groups. However, in NACT group, those with low B7-H4 expression had significantly longer OS (P = 0.031). The study findings suggest that low expression of B7-H4 could serve as a candidate biomarker for predicting response to NACT and could provide favorable prognostic information in GC.

Potential targeting of B7‐H4 for the treatment of cancer

“…Recent studies have demonstrated various cancer cells and tissues overexpress B7‐H4 protein, and that B7‐H4 protein expression within tumors correlates with various pathological and clinical characteristics. The expression level of B7‐H4 protein in ovarian cancer is related to cancer types, cancer stage, the numbers of Tregs, and patient survival .…”

Generation of avian-derived anti-B7-H4 antibodies exerts a blockade effect on the immunosuppressive response

“…The protein has been found capable of affecting cytokine secretion, T-cell activation, and cytotoxicity abilities [ 5 , 6 ]. B7-H4 has been found in human tumors; in addition to serving as a potential treatment indicator [ 7 , 8 , 9 , 10 ], soluble B7-H4 has been recognized as a possible biomarker for cancer diagnosis [ 11 , 12 ]. Clinical research also revealed that relative to B7-H4+ tumors, B7-H4− tumors are larger (on average) and occur in patients with higher TNM stages [ 13 ].…”

Reduction in Peripheral CD19+CD24hCD27+ B Cell Frequency Predicts Favourable Clinical Course in XELOX-Treated Patients with Advanced Gastric Cancer

“…In gastric cancer patients, intratumoural infiltrations of cytotoxic T cells and memory cells were shown to indicate better prognoses and survival outcomes [17], while patients with higher tumour-associated microphage (TAM) infiltration had worse surgical outcomes [18,19]. Maskey et al assessed the immune response in gastric cancer patients after neoadjuvant chemotherapy (NACT) and found that those with a low expression of B7-H4 in their tumours had significantly longer OS [20]. Furthermore, the density of mast cell-derived IL-17 had significant positive correlations with microvessels, neutrophils, and regulatory T cells (Tregs).…”