Transplantation of iPS-Derived Tumor Cells with a Homozygous MHC Haplotype Induces GRP94 Antibody Production in MHC-Matched Macaques

Cancer Res. 2017 Nov 1;77(21):6001-6010. doi: 10.1158/0008-5472.CAN-17-0775. Epub 2017 Sep 7.


Immune surveillance is a critical component of the antitumor response in vivo, yet the specific components of the immune system involved in this regulatory response remain unclear. In this study, we demonstrate that autoantibodies can mitigate tumor growth in vitro and in vivo We generated two cancer cell lines, embryonal carcinoma and glioblastoma cell lines, from monkey-induced pluripotent stem cells (iPSC) carrying a homozygous haplotype of major histocompatibility complex (MHC, Mafa in Macaca fascicularis). To establish a monkey cancer model, we transplanted these cells into monkeys carrying the matched Mafa haplotype in one of the chromosomes. Neither Mafa-homozygous cancer cell line grew in monkeys carrying the matched Mafa haplotype heterozygously. We detected in the plasma of these monkeys an IgG autoantibody against GRP94, a heat shock protein. Injection of the plasma prevented growth of the tumor cells in immunodeficient mice, whereas plasma IgG depleted of GRP94 IgG exhibited reduced killing activity against cancer cells in vitro These results indicate that humoral immunity, including autoantibodies against GRP94, plays a role in cancer immune surveillance. Cancer Res; 77(21); 6001-10. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantibodies / metabolism
  • Carcinoma, Embryonal / genetics
  • Carcinoma, Embryonal / immunology
  • Carcinoma, Embryonal / pathology
  • Cell Line, Tumor
  • Cells, Cultured
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / immunology
  • Glioblastoma / pathology
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / immunology*
  • HSP70 Heat-Shock Proteins / metabolism
  • Haplotypes
  • Homozygote
  • Induced Pluripotent Stem Cells / immunology*
  • Induced Pluripotent Stem Cells / metabolism
  • Macaca fascicularis
  • Major Histocompatibility Complex / genetics
  • Major Histocompatibility Complex / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Mice
  • Neoplasm Transplantation / methods
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology


  • Autoantibodies
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • glucose-regulated proteins