Sharma Padmanee, Shen Yu, Wen Sijin, Yamada Sachiko, Jungbluth Achim A, Gnjatic Sacha, Bajorin Dean F, Reuter Victor E, Herr Harry, Old Lloyd J, Sato Eiichi
Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3967-72. doi: 10.1073/pnas.0611618104. Epub 2007 Feb 27.
Tumor-infiltrating cytotoxic T lymphocytes (TILs), including CD8 TILs, have been associated with favorable clinical outcomes in multiple tumor types. Tumor-infiltrating CD8 T cells and major histocompatibility complex (MHC) class I expression in urothelial carcinoma (UC) have not been previously reported. Most immune responses are mediated by local cytotoxic lymphocytes (CD8 T cells), which can eradicate tumor cells by recognizing tumor-associated antigens presented by MHC class I molecules. Here we analyzed the presence of intratumoral CD8 T cells, the expression of MHC class I antigen, and the expression of the NY-ESO-1 tumor antigen in UC samples and correlated our findings with clinical outcome. Immunohistochemical staining for intratumoral CD8 T cells in tissue samples from 69 patients with UC showed that patients with advanced UC (pT2, pT3, or pT4) and higher numbers of CD8 TILs within the tumor (> or =8) had better disease-free survival (P < 0.001) and overall survival (P = 0.018) than did patients with similar-staged UC and fewer intratumoral CD8 TILs. We conclude that the extent of intratumoral CD8 TILs is an important prognostic indicator in advanced UC.
肿瘤浸润性细胞毒性T淋巴细胞（TILs），包括CD8 TILs，已被证明与多种肿瘤类型的良好临床结果相关。尿路上皮癌（UC）中肿瘤浸润性CD8 T细胞和主要组织相容性复合体（MHC）I类分子的表达此前尚未见报道。大多数免疫反应由局部细胞毒性淋巴细胞（CD8 T细胞）介导，这些细胞可通过识别MHC I类分子呈递的肿瘤相关抗原来清除肿瘤细胞。在此，我们分析了UC样本中瘤内CD8 T细胞的存在情况、MHC I类抗原的表达以及NY-ESO-1肿瘤抗原的表达，并将我们的发现与临床结果相关联。对69例UC患者组织样本中的瘤内CD8 T细胞进行免疫组织化学染色显示，晚期UC（pT2、pT3或pT4）患者且肿瘤内CD8 TIL数量较多（≥8个）的患者，其无病生存期（P < 0.001）和总生存期（P = 0.018）均优于分期相似但瘤内CD8 TIL数量较少的UC患者。我们得出结论，瘤内CD8 TILs的程度是晚期UC的一个重要预后指标。
