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Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma
Author(s) -
Ohno Satoshi,
Tachibana Mitsuo,
Fujii Toshiyuki,
Ueda Shuhei,
Kubota Hirofumi,
Nagasue Naofumi
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10144
Subject(s) - stromal cell , cd8 , immune system , stroma , medicine , pathology , apoptosis , cancer research , cancer , tumor microenvironment , immunology , biology , immunohistochemistry , biochemistry
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. © 2001 Wiley‐Liss, Inc.