ALTERATION OF SIGNAL-TRANSDUCING MOLECULES IN TUMOR-INFILTRATING LYMPHOCYTES AND PERIPHERAL-BLOOD T-LYMPHOCYTES FROM HUMAN COLORECTAL-CARCINOMA PATIENTS

Tumor development or growth is accompanied by impaired immune response s, such as a poor proliferative response or down-regulated cytolytic T lymphocyte activity. Although recent reports have suggested that modi fication of the signal-transducing molecule is responsible for impaire d immune responses in tumor-bearing hosts, the causes of defective imm une function are not yet completely understood. Furthermore, the clini cal significance of the findings is not yet clear. In this study, we i nvestigated the alteration of several signal-transducing molecules In peripheral blood T lymphocytes (T-PBL) as well as in tumorinfiltrating lymphocytes (TIL) from human colorectal carcinoma patients and their relationship with the impaired host immune responses. A greater reduct ion in CD3 zeta chain level was observed in TIL than in T-PBL from tum or-bearing hosts. CD3 zeta chain reduction in T-PBL correlated with th e clinicopathological stage of a tumor, especially with the status of lymph node metastasis. The levels of p56(lck) and p59(fyn) protein tyr osine kinase in T-PBL were also compared between tumor-bearing hosts a nd normal healthy volunteer. In T-PBL from tumor-bearing hosts, expres sion of protein tyrosine kinase p59(fyn) was significantly lower than that of p56(lck). However, the level of CD3 zeta chain expression did not correlate with T lymphocyte functions such as T lymphocyte prolife rative response or allogeneic target cell lysis.