Okada K, Komuta K, Hashimoto S, Matsuzaki S, Kanematsu T, Koji T
Department of Surgery II, Nagasaki University School of Medicine, Japan.
Clin Cancer Res. 2000 Sep;6(9):3560-4.
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 per 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 higher than that of colorectal carcinoma without metastasis. The cases with a high LI of 212.0 had a significantly poorer prognosis than those with a low LI. We also confirmed immunohistochemically that a part of the TILs expressed Fas using the sections adjacent to what contained 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 frequently in FasL-positive cases than in FasL-negative ones. These findings indicate 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 counterattack. This tumor immune evasion induced by FasL may therefore affect the malignant potential of human colorectal carcinoma.
我们通过原位缺口平移法（ISNT）研究了从41例结直肠癌中获取的肿瘤浸润淋巴细胞（TIL）的凋亡情况。当将ISNT标记指数（LI）确定为组织切片中每1000个TIL细胞核中的阳性细胞核数量时，LI中位数为12.0（范围为2 - 30）。有淋巴结转移的结直肠癌的ISNT LI高于无转移的结直肠癌。LI≥212.0的病例预后明显比LI低的病例差。我们还通过免疫组织化学方法，利用含有大量ISNT阳性TIL的切片相邻的切片证实了部分TIL表达Fas。此外，在61%的病例中，在结肠癌细胞的细胞表面以及细胞质中检测到Fas配体（FasL）表达。FasL阳性病例中TIL的凋亡始终比FasL阴性病例更频繁地出现。这些发现表明，结肠癌细胞中表达的FasL可能通过一种称为Fas反击的Fas - FasL系统杀死Fas阳性的免疫效应TIL。因此这种由FasL诱导的肿瘤免疫逃逸可能会影响人类结直肠癌的恶性潜能。
