Cutaneous tumors cease CXCL9/Mig production as a result of IFN-?-mediated immunoediting.

Authors:
Petro M1, Kish D, Guryanova OA, Ilyinskaya G, Kondratova A, Fairchild RL, Gorbachev AV.
In:
Source: J Immunol
Publication Date: (2013)
Issue: 190(2): 832-41
Research Area:
Immunotherapy / Hematology
Basic Research
Culture Media:
Experiment

Tumor-reactive T cell activation in T cell–transferred RAG12/2 mice: Tumor-draining lymph nodes were removed on day 14 after tumor implant from control RAG12/2 recipients or from T cell–transferred RAG12/2 recipients of Mig-expressing or Mig-deficient tumors (designated as Mig+ and Mig2 tumors, respectively). Aliquots of 5x10exp5 cells were cultured with mitomycin-treated tumor cells, and numbers of IFN-gamme producing cells were assessed by ELISPOT using HL-1 culture medium, as previously described

Abstract

During growth in the host, tumor cells are subjected to the stresses of innate and adaptive immunity (immunoediting), which provoke epigenetic changes in the tumor and increase tumor resistance to these immune responses. Our recent studies in methylcholanthrene-induced fibrosarcomas have indicated the appearance and rapid growth of tumor variants deficient in producing the T cell chemoattractant chemokine CXCL9/Mig, an important component of antitumor immunity. In the current report, we demonstrate that highly tumorigenic Mig-deficient tumor variants arise in both cutaneous fibrosarcoma and melanoma as a result of immune stress imposed by IFN-? and T cells. The consequence of the loss of tumor-derived Mig expression is the increased resistance of Mig-deficient tumors to T cell-mediated immunity, which promotes the accelerated growth of these tumor variants. Remarkably, the ability of Mig-deficient tumor cells to express another CXCR3 ligand, CXCL10/IFN-?-inducible protein, does not compensate for the absent antitumor functions of Mig, suggesting a nonredundant role for this chemokine in the suppression of tumor growth. To our knowledge, these studies report for the first time that IFN-?-mediated stress leads to the loss of specific chemokine expression by tumor cells, which in turn promotes tumor growth and evasion of the immune response.