Role of Tumor-associated Macrophages (TAM) in Advanced Gastric Carcinoma: The Impact on FasL-mediated Counterattack

Background: Exactly what role does tumor-derived Fas ligand (FasL) play in cancer: maintaining the immune privilege site or inducing a pro-inflammatory effect? One possible hypothesis is that tumor-associated macrophages (TAM) act as the mediator that enables apoptosis of anti-tumor immune cells without FasL-related inflammation. We have evaluated the tumor FasL expression and TAM along the tumor margin and/or in cancer stroma, and their impact on the infiltration of immune-competent cells into the tumor nest. Patients and Methods: Tissue specimens from consecutive 84 advanced gastric carcinoma patients, who had undergone a curative resection, were evaluated for TAM (CD68+ cells), tumor FasL expression and immune status (CD8+ T cells). Results: A high number of TAM significantly correlated with lymph node metastasis, intestinal type tumor and FasL expression. Although TAM had a tendency for an inverse correlation with the number of CD8+ T cells within the tumor nest (nest CD8) (p=0.0592), there was no correlation between FasL expression and nest CD8 (p=0.2158). This inverse association was found to be stronger in cases with both FasL-positive and high TAM tumors than in others (p=0.0139). The combination parameter of FasL-positive and high TAM became an independent prognostic factor in Cox's multivariate analysis, along with the pT status, nest CD8 and tumor cell apoptosis. Conclusion: We suggest that TAM works harmoniously with tumor-derived FasL and serves as a barrier against the infiltration of CD8+ T cells into the cancer nest.