Perrin P, Cassagnau E, Burg C, Patry Y, Vavasseur F, Harb J, Le Pendu J, Douillard J Y, Galmiche J P, Bornet F
INSERM Contrat Jeune Formation 90-11, Institute of Biology, University of Medicine, Nantes, France.
Gastroenterology. 1994 Dec;107(6):1697-708. doi: 10.1016/0016-5085(94)90810-9.
BACKGROUND/AIMS: Immunotherapy using interleukin 2 has had disappointing results in the treatment of colon cancer. Overcoming escape mechanisms, such as lack of antigen presentation and absence of accessory adhesion molecules on cancer cells, may increase its efficiency. We tried to do so by modifying the phenotype of the weakly immunogenic rat colon cancer PROb cells with sodium butyrate.
After in vitro treatment with butyrate, PROb cells were tested for lymphokine-activated killer cell sensitivity and, using cytofluorometry, expression of adhesion molecules. We then treated established PROb peritoneal carcinomatoses with intraperitoneal injections of interleukin 2 and butyrate. Tumors were studied histologically and immunohistochemically. We tested the specificity of the immune protection by subsequent subcutaneous challenges with either PROb or glioma cells and by Winn's assay.
Butyrate increased lymphokine-activated killer cell sensitivity and expression of major histocompatibility complex class I and intercellular adhesion molecule 1 in vitro. Interleukin 2/butyrate combination resulted in cases of complete cure of carcinomatosis with specific protection against PROb cells. We noticed a complex stroma reaction with numerous functional antigen presenting cells close to PROb cells.
The complete regression of tumor masses may be attributed, at least in part, to a butyrate-induced increase in immunogenicity of the cancer cells. This new combined immunotherapy may be of interest in the treatment of colon cancer.
背景/目的：使用白细胞介素2进行免疫治疗在结肠癌治疗中效果不佳。克服逃逸机制，如缺乏抗原呈递和癌细胞上缺乏辅助黏附分子，可能会提高其疗效。我们试图通过用丁酸钠改变弱免疫原性大鼠结肠癌PROb细胞的表型来实现这一点。
用丁酸盐体外处理PROb细胞后，检测其对淋巴因子激活的杀伤细胞的敏感性，并使用细胞荧光术检测黏附分子的表达。然后，我们通过腹腔注射白细胞介素2和丁酸盐来治疗已形成的PROb腹膜癌。对肿瘤进行组织学和免疫组织化学研究。我们通过随后用PROb或胶质瘤细胞进行皮下攻击以及温氏试验来测试免疫保护的特异性。
丁酸盐在体外增加了淋巴因子激活的杀伤细胞敏感性以及主要组织相容性复合体I类和细胞间黏附分子1的表达。白细胞介素2/丁酸盐联合治疗导致部分腹膜癌病例完全治愈，并对PROb细胞具有特异性保护作用。我们注意到在PROb细胞附近有复杂的基质反应，伴有大量功能性抗原呈递细胞。
肿瘤块的完全消退至少部分可归因于丁酸盐诱导的癌细胞免疫原性增加。这种新的联合免疫疗法可能对结肠癌治疗有意义。
