Frequency of apoptosis of tumor-infiltrating lymphocytes induced by Fas counterattack in human colorectal carcinoma and its correlation with prognosis

We investigated apoptosis in tumor-infiltrating lymphocytes (TILs) obtained from 41 colorectal carcinomas by in situ nick translation (ISNT). When the ISNT labeling index (LI) was determined as the number of positive nuclei p er 1000 nuclei of TIL in tissue sections, the median LI was 12.0 (range, 2- 30). The ISNT LI of colorectal carcinoma with lymph node metastasis was hig her than that of colorectal carcinoma without metastasis. The cases with a high LI of greater than or equal to 12.0 had a significantly poorer prognos is than those with a low LI, We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contain ed abundant ISNT-positive TILs. Moreover, Fas ligand (FasL) expression was detected on the cell surface as well as the cytoplasm of colorectal cancer cells in 61% of cases. Apoptosis in TILs was consistently seen more frequen tly in FasL-positive cases than in FasL-negative ones. These findings indic ate that the FasL expressed in colorectal carcinoma cells may kill the Fas- positive immune effective TILs by means of a Fas-FasL system termed Fas cou nterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.