Immunopotentiating role of IFN-gamma in early and late stages of type 1 CD8 effector cell-mediated tumor rejection

Clin Immunol. 2001 Jan;98(1):70-84. doi: 10.1006/clim.2000.4945.


Type 1 cytolytic CD8 effector T cells (Tc1) characteristically secrete IFN-gamma. Using an OVA-transfected B16 melanoma lung tumor model, we show that OVA Ag-specific Tc1 cells mediate a reduction in tumor growth that significantly prolongs survival in tumor-bearing mice. Transfer of Tc1 cells from OT-I mice crossed to IFN-gamma-KO mice showed that IFN-gamma-deficient Tc1 effector cells were less therapeutically effective than corresponding cells from wildtype mice. Therapeutic effects were dependent, in part, on effector cell-derived IFN-gamma, which not only induced elevated levels of lung-derived IP-10 and RANTES chemokine message in vivo, but also increased the local accumulation of activated host-derived CD4(+)/CD44(High), CD8(+)/CD44(High), and non-T-immune cell populations at the tumor site. Over time, the numbers of host-derived immune cells increased in the lung, which correlated with an elevated production of IP-10 and RANTES and a continued reduction in tumor burden. Conversely, donor Tc1 cell numbers markedly diminished at corresponding times, suggesting that prolonged therapeutic responses were due to the presence of host-derived antitumor mechanisms. Moreover, adoptive transfer of IFN-gamma-deficient Tc1 cells into tumor-bearing IFN-gamma-KO recipients showed that both recipient and donor-derived IFN-gamma play a significant role in Tc1-mediated responses and that Tc1 effector cell immunotherapy is predominantly mediated by IFN-gamma-dependent mechanisms.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology
  • CD8-Positive T-Lymphocytes / immunology*
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / physiology
  • Epitopes
  • Female
  • Immunotherapy*
  • Inflammation Mediators / pharmacology
  • Interferon-gamma / immunology*
  • Lung Neoplasms / prevention & control*
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin / immunology
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured
  • Up-Regulation


  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Chemokine CCL5
  • Epitopes
  • Inflammation Mediators
  • RNA, Messenger
  • Interferon-gamma
  • Ovalbumin