Eto Masatoshi, Harada Mamoru, Tatsugami Katsunori, Harano Masahiko, Koga Hirofumi, Matsuzaki Goro, Naito Seiji
Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
BJU Int. 2005 Feb;95(3):421-4. doi: 10.1111/j.1464-410X.2005.05313.x.
To determine whether heat-shock protein (HSP) 60-recognizing CD4(+) T cells show antitumour activity against renal carcinoma (RENCA) cells, as HSP is highly expressed by tumour cells and induced in cells by various stresses, including transformation.
RENCA, a renal cortical adenocarcinoma cell line of BALB/c origin, was used. Expression of major histocompatibility complex (MHC) class I, class II and HSP-60 on RENCA tumour cells was analysed by flow cytometry. BASL1.1, an autoreactive T-helper type 1 type CD4(+) T cell clone established by us, and that recognises HSP-60, was also used for a tumour-neutralising assay.
The RENCA cells were negative for MHC class II, but expressed intracellular HSP-60. In the tumour-neutralising assay, BASL1.1 cells significantly suppressed the in vivo growth of RENCA cells. Three of five mice rejected RENCA cells when co-inoculated with BASL1.1 cells.
These results indicate that HSP-60-recognizing CD4(+) T cells have the potential to eliminate renal cell carcinoma in vivo and that the eliciting of an anti-self T cell response at the tumour site can lead to regression of renal cancer.
鉴于热休克蛋白(HSP)在肿瘤细胞中高表达且可由包括转化在内的各种应激在细胞中诱导产生,确定识别HSP60的CD4(+) T细胞是否对肾癌细胞(RENCA)具有抗肿瘤活性。
使用源自BALB/c的肾皮质腺癌细胞系RENCA。通过流式细胞术分析RENCA肿瘤细胞上主要组织相容性复合体(MHC)I类、II类和HSP - 60的表达。我们建立的识别HSP - 60的自身反应性辅助性T1型CD4(+) T细胞克隆BASL1.1也用于肿瘤中和试验。
RENCA细胞MHC II类呈阴性,但表达细胞内HSP - 60。在肿瘤中和试验中,BASL1.1细胞显著抑制RENCA细胞的体内生长。五只小鼠中有三只在与BASL1.1细胞共同接种时排斥RENCA细胞。
这些结果表明,识别HSP - 60的CD4(+) T细胞具有在体内消除肾细胞癌的潜力,并且在肿瘤部位引发抗自身T细胞反应可导致肾癌消退。