Pimm M V, Baldwin R W
Int J Cancer. 1977 Jul 15;20(1):37-43. doi: 10.1002/ijc.2910200108.
The immunogenicities of in vivo lines established from primary MCA-induced rat sarcomas have been compared with those of lines initiated from tumour recurrences at the site of the primaries' surgical excisions. Lines from two of four primary sarcomas showed little or no immunogenicity, as assessed by protection against challenge afforded by graft excision or implantation of irradiated tissue. In contrast, lines from all four recurrences were immunogenic, giving protection against up to 5 X 10(6) tumour cells. Most importantly, with all four tumours, lines established from recurrences were antigenically distinct from lines derived from their original primary sarcomas, so that immunization with regrowth lines gave no protection against the lines from the primaries, and vice versa. These studies demonstrate that primary MCA-induced sarcomas are antigenically distinct from recurrent tumors arising after surgical removal of the primaries, implying that these tumours arose by clonal amplification of separate populations of transformed cells. This may reflect proliferation of dormant neoplastic cells or the further induction of transformed cells by residual carcinogen. These findings are relevant to the multifocal origin of tumours and for the design of active immunotherapy for the treatment of recurrences or metastatic deposits.
已将从原发性N-甲基-N-亚硝基脲(MCA)诱导的大鼠肉瘤建立的体内细胞系的免疫原性,与从原发性肿瘤手术切除部位的肿瘤复发中起始的细胞系的免疫原性进行了比较。通过移植切除或植入经辐照的组织所提供的针对攻击的保护作用评估,四个原发性肉瘤中的两个的细胞系显示出很少或没有免疫原性。相比之下,来自所有四个复发肿瘤的细胞系都具有免疫原性,可针对多达5×10⁶个肿瘤细胞提供保护。最重要的是,对于所有四个肿瘤,从复发肿瘤建立的细胞系在抗原性上与源自其原始原发性肉瘤的细胞系不同,因此用再生细胞系进行免疫不能对原发性细胞系提供保护,反之亦然。这些研究表明,原发性MCA诱导的肉瘤在抗原性上与原发性肿瘤手术切除后出现的复发肿瘤不同,这意味着这些肿瘤是由不同群体的转化细胞的克隆扩增产生的。这可能反映了休眠肿瘤细胞的增殖或残留致癌物对转化细胞的进一步诱导。这些发现与肿瘤的多灶性起源以及用于治疗复发或转移灶的主动免疫疗法的设计有关。