Immune effectors responsible for the elimination of hyperploid cancer cells

OncoImmunology

Isabelle Martins¹  Pauline Garcia¹  Chloé Bordenave¹  Laura Senovilla¹  Norma Bloy¹  Guido Kroemer¹  Fernando Aranda¹  Kariman Chaba¹  Gautier Stoll¹  Antoine Tesniere² 

[1] INSERM U1138-Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers;Paris Descartes University;

关键词: hyperploidy;    genomic instability;    cancer;    immunosurveillance;    immunoselection;   

DOI  :  10.1080/2162402X.2018.1463947

来源: DOAJ

【 摘 要 】

The immune system avoids oncogenesis and slows down tumor progression through a mechanism called immunosurveillance. Nevertheless, some malignant cells manage to escape from immune control and form clinically detectable tumors. Tetraploidy, which consists in the intrinsically unstable duplication of the genome, is considered as a (pre)-cancerous event that can result in aneuploidy and contribute to oncogenesis. We previously described the fact that tetraploid cells can be eliminated by the immune system. Here, we investigate the role of different innate and acquired immune effectors by inoculating hyperploid cancer cells into wild type or mice bearing different immunodeficient genotypes (Cd1d−/−, FcRn−/−, Flt3l−/−, Foxn1nu/nu, MyD88−/−, Nlrp3−/−, Ighmtm1Cgn, Rag2−/−), followed by the monitoring of tumor incidence, growth and final ploidy status. Our results suggest that multiple different immune effectors including B, NK, NKT and T cells, as well as innate immune responses involving the interleukine-1 receptor and the Toll-like receptor systems participate to the immunoselection against hyperploid cells. Hence, optimal anticancer immunosurveillance likely involves the contribution of multiple arms of the immune system.

【 授权许可】

Unknown