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 response. Their aberrant expression either by the tumor cells or by the tumor infiltrating lymphocytes confers a selective advantage to the tumor to grow and suppress the cytotoxic activity of the infiltrating lymphocytes. Therefore, analysis of these soluble factors in the tumor microenvironment can provide an insight into the understanding of the tumor behavior and may be used as a prognostic factor. In the present study the nature of the tumor infiltrating lymphocytes (TILs) and cytokine profile was examined in 36 and 19 mammary carcinoma tissues, respectively, by immunohistochemistry and PCR. Phenotypic differences in the number of cytotoxic T lymphocytes (CD8+) and lymphokine activated killer cells (CD16) was observed among TILs when patients with either early disease stage (39% and 46.6%, respectively) or those alive with no 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 samples for cytokine mRNA expression by RT-PCR revealed the presence of TNF-alpha, IL-10, TGF-beta1, and IL-2. However, semi-quantitative PCR analysis demonstrated TGF-beta1 expression to be significantly higher in patients with a favorable outcome (1.0246 attomoles/micromoles) as compared to patients with a poor prognosis (0.1157 attomoles/micromoles). Our results demonstrate the potential biological significance of certain host factors, particularly TILs and TGFbeta1 expression, on the outcome of breast cancer.