Ménoret A, Patry Y, Burg C, Le Pendu J
INSERM Unit 419, Biology Institute, Nantes, France.
J Immunol. 1995 Jul 15;155(2):740-7.
Recent results have shown the importance of heat-shock proteins (hsp) in immune reactions. In addition, immunization against hsp purified from some immunogenic tumors specifically protects animals from a challenge with the tumor from which the hsp were purified. The protection is dependent on the association between hsp and immunogenic peptides. Using a model of rat colon carcinoma, we studied the importance of hsp70 expression in determining the tumorigenicity of cancer cells in immunocompetent syngeneic animals. Various clones with distinct tumorigenic potentials have been derived from the same parental tumor. Some clones are tumorigenic and others are rejected through an immune-based mechanism. It was observed that among all parameters tested, immunogenicity of tumors co-segregated with expression of inducible hsp70 but not with constitutive hsc70. Variants were obtained from a highly tumorigenic clone (PROb) and from a regressive clone (REGb). The PROb variant (Ph8), selected by repeated sublethal heat shocks, showed an increased capacity for hsp70 synthesis concomitant with a decreased tumorigenicity. Inversely, the REGb variant (REGR73), selected after in vivo growth in partially immunosuppressed rats, acquired tumorigenicity and lost the ability to synthesize hsp70. Expression of other immunologic mediators such as intercellular adhesion molecule-1, MHC I, and MHC II did not co-segregate with tumor immunogenicity. Depletion experiments showed that the immunity elicited by these tumors involves TCR-alpha beta-bearing T cells. Such observations imply that, in this experimental model, inducible but not constitutive hsp70 is involved in immunogenicity of tumors.
近期研究结果表明热休克蛋白（hsp）在免疫反应中具有重要作用。此外，用从某些免疫原性肿瘤中纯化的hsp进行免疫，可特异性保护动物免受纯化hsp所源自肿瘤的攻击。这种保护作用依赖于hsp与免疫原性肽之间的关联。我们利用大鼠结肠癌模型，研究了hsp70表达在免疫健全的同基因动物中对癌细胞致瘤性的影响。从同一亲本肿瘤衍生出了具有不同致瘤潜力的各种克隆。一些克隆具有致瘤性，而另一些则通过基于免疫的机制被排斥。结果发现，在所有检测参数中，肿瘤的免疫原性与诱导型hsp70的表达共分离，而与组成型hsc70无关。从高致瘤性克隆（PROb）和消退性克隆（REGb）获得了变体。通过反复亚致死热休克选择的PROb变体（Ph8），hsp70合成能力增强，同时致瘤性降低。相反，在部分免疫抑制大鼠体内生长后选择的REGb变体（REGR73）获得了致瘤性并丧失了合成hsp70的能力。其他免疫介质如细胞间黏附分子-1、MHC I和MHC II的表达与肿瘤免疫原性不共分离。清除实验表明，这些肿瘤引发的免疫涉及携带TCR-αβ的T细胞。这些观察结果表明，在这个实验模型中，诱导型而非组成型hsp70参与了肿瘤的免疫原性。
