Association between fibroblast activation protein α expression and immune environment in gastric cancer

Tumor stroma serves an important role in cancer progression. However, the role of fibroblast activation protein α (FAP), a subpopulation marker of cancer-associated fibroblasts (CAFs), remains poorly understood, especially in gastric cancer. The present study investigated the role of FAP-positive CAFs in gastric cancer prognosis and immune environment. The retrospective study included patients with gastric cancer who underwent curative resection. The tumor-stroma ratio (TSR) and FAP expression status were evaluated using immunohistochemistry, after which their associations with recurrence-free survival (RFS) were investigated. In addition, immune cell infiltration was evaluated, including T cells, regulatory T cells (Tregs) and M2 macrophages, using immunohistochemistry, and its association with TSR or FAP status was analyzed. Among the 128 eligible patients, 29 (23%) had low TSR, whereas 39 (30%) were FAP-positive. No significant association was observed between TSR and FAP status (P=0.596). The low TSR group and FAP-positive group showed significantly worse survival than the high TSR group and FAP-negative group (log-rank P=0.004, P=0.011, respectively). Subsequently, a Cox multivariate analysis for RFS identified that FAP positivity was an independent factor for poor prognosis (P=0.009) but low TSR was not (P=0.088). FAP-positive patients had a higher tumor infiltrating FOXP3⁺ Tregs/CD3⁺ T-cell ratio (P<0.001) and FOXP3⁺ Tregs/CD8⁺ T-cell ratio (P=0.006), and higher levels of CD163⁺ M2 macrophages (P=0.011) compared with FAP-negative patients, although such differences were not observed according to TSR status. In conclusion, the present study revealed that FAP status may be an independent prognostic factor in gastric cancer, potentially contributing to the formation of immune tolerance within the tumor microenvironment.