STUDY OF TUMOR-INFILTRATING LYMPHOCYTES AND TRANSFORMING-GROWTH-FACTOR-BETA AS PROGNOSTIC FACTORS IN BREAST-CARCINOMA

Cytokines and growth factors are powerful modulators of the immune res ponse, Their aberrant expression either by the tumor cells or by the t umor infiltrating lymphocytes confers a selective advantage to the tum or to grow and suppress the cytotoxic activity of the infiltrating lym phocytes. Therefore, analysis of these soluble factors in the tumor mi croenvironment can provide an insight into the understanding of the tu mor behavior and may be used as a prognostic factor, In the present st udy the nature of the tumor infiltrating lymphocytes (TILs) and cytoki ne profile was examined in 36 and 19 mammary carcinoma tissues, respec tively, by immunohistochemistry and PCR. Phenotypic differences in the number of cytotoxic T lymphocytes (CD8(+)) and lymphokine activated k iller cells (CD16) was observed among TILs when patients with either e arly disease stage (39% and 46.6%, respectively) or those alive with n o residual disease (31% and 52%, respectively) were compared with late stage (9.7% and 22.8%, respectively) or those dead of disease (14.6% and 15.6%, respectively). Furthermore, analysis of the 19 tumor sample s for cytokine mRNA expression by RT PCR revealed the presence of TNF- alpha, IL-10, TGF-beta 1, and IL-2, However, semi-quantitative FCR ana lysis demonstrated TGF-beta 1 expression to be significantly higher in patients with a favorable outcome (1.0246 attomoles/mu moles) as comp ared to patients with a poor prognosis (0.1157 attomoles/mu moles), Ou r results demonstrate the potential biological significance of certain host factors, particularly TILs and TGF beta 1 expression, on the out come of breast cancer. (C) 1997 Wiley-Liss, Inc.