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Int J Cancer. 2002 Feb 20;97(6):770-4.

Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma.

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Second Department of Surgery, Shimane Medical University, Shimane, Japan.


Although several hypotheses have been proposed explaining the mechanisms of the immune-privileged status of malignant tumors, the exact pathway is yet to be explored. Tumor stroma plays a vital role in the prognosis of cancer patients; however, the immunomodulatory impact of gastric cancer stroma has not been reported. We have evaluated the amount of stromal collagen and its impact on the infiltration of immune-competent cells into the tumor cell nest in gastric carcinoma. Tissue specimens from 84 advanced gastric carcinoma patients who had undergone a curative resection were evaluated for host immune status (CD8+ T cells), tumor stromal reaction (AZAN staining), tumor Fas ligand expression and incidence of tumor cell apoptosis (by TUNEL). The number of apoptotic tumor cells (apoptotic index [AI]) increased proportionally with an increase in the number of CD8+ T cells within the cancer cell nest (nest CD8) (p = 0.0001). Nest CD8 was inversely correlated with the amount of stromal collagen (p < 0.0001). Nest CD8 and AI became independent predictors of patient survival (p = 0.0023 and p = 0.044, respectively) in Cox's multivariate analysis. The amount of stromal collagen was found to be a significant predictor of disease relapse in univariate analysis (p = 0.0010) but not in multivariate analysis (p = 0.4729). In conclusion, increased nest CD8 produced a survival advantage by inducing tumor cell apoptosis in gastric carcinoma patients. Increased tumor stromal collagen worked as a barrier for CD8+ T-cell infiltration and might be one of the mechanisms of tumor escape from the host immune attack.

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