Differently immunogenic cancers in mice induce immature myeloid cells that suppress CTL in vitro but not in vivo following transfer


  • K. Schmidt
  • S. Zilio
  • J.C. Schmollinger
  • V. Bronte
  • T. Blankenstein
  • G. Willimsky


  • Blood


  • Blood 121 (10): 1740-1748


  • Tumors frequently induce immature myeloid cells (iMC), which suppress specific and unrelated cytotoxic T lymphocyte (CTL) responses and are termed myeloid derived suppressor cells (MDSC). Mainly analyzed by in vitro assays in tumor transplantation models, little is known about their function in autochthonous tumor models in vivo. We analyzed iMC in three SV40 large T (Tag)-driven conditional autochthonous cancer models with drastically different immune status: 1. Early Tag-specific CTL competence and rare stochastic Tag activation leading to sporadic cancer, which induces an aberrant immune response and CTL tolerance. 2. Cre/LoxP recombinase-mediated hepatocellular carcinoma (HCC) development in neonatal Tag-tolerant mice. 3. Tag-activation through Cre recombinase-encoding viruses in the liver and HCC development with systemic anti-Tag CTL immunity. In the first but not the two latter models, tumors induced CTL hypo-responsiveness to tumor unrelated antigens. Regardless of the model, tumors produced IL-6 and VEGF but not GM-CSF and induced iMC (CD11b(+)Gr-1(int)) that suppressed CTL responses in vitro. None of the iMC from the different tumor models suppressed CTL responses in adoptive cell transfer experiments, unless GM-CSF was provided in vivo. Together, iMC expand independent of the type of anti-tumor response and are not immune-suppressive in a cell-autonomous fashion.