Cancer Immunology, Immunotherapy

, 60:1473

Th17 and Th17-stimulated CD8+ T cells play a distinct role in Th17-induced preventive and therapeutic antitumor immunity

  • Manjunatha Ankathatti Munegowda
  • Yulin Deng
  • Sean J. Mulligan
  • Jim Xiang
Original article

DOI: 10.1007/s00262-011-1054-y

Cite this article as:
Ankathatti Munegowda, M., Deng, Y., Mulligan, S.J. et al. Cancer Immunol Immunother (2011) 60: 1473. doi:10.1007/s00262-011-1054-y

Abstract

CD4+ Th17 cells induce antitumor immunity leading to the eradication of established tumors. However, the mechanism of antitumour immunity and CTL activation by Th17 cells and the distinct role of Th17 and Th17-activated CTLs in antitumor immunity are still elusive. In this study, we generated ovalbumin (OVA)-specific Th17 cells by cultivating OVA-pulsed dendritic cells with CD4+ T cells derived from transgenic OTII mice in the presence of IL-6, IL-23, TGF-β, and anti-IFN-γ antibody. We demonstrated that Th17 cells acquired major histocompatibility complex/peptide (pMHC)-I and expressed RORγt, IL-17, and IL-2. Th17 cells did not have any direct in vitro tumor cell–killing activity. However, Th17 cells were able to stimulate CD8+ CTL responses via IL-2 and pMHC I, but not IL-17 signaling, which play a major role in Th17-induced preventive immunity against OVA-expressing B16 melanoma. Th17 cells stimulated the expression of CCL2 and CCL20 in lung tumor microenvironments promoting the recruitment of various inflammatory leukocytes (DCs, CD4+, and CD8+ T cells) stimulating more pronounced therapeutic immunity for early-stage (5-day lung metastases or 3 mm, s.c.) tumor than for well-established (6 mm, s.c.) tumor. The therapeutic effect of Th17 cells is associated with IL-17 and is mediated by Th17-stimulated CD8+ CTLs and other inflammatory leukocytes recruited into B16 melanoma via Th17-stimulated CCL20 chemoattraction. Taken together, our data elucidate a distinct role of Th17 and Th17-stimulated CD8+ CTLs in the induction of preventive and therapeutic antitumor immunity, which may greatly impact the development of Th17-based cancer immunotherapy.

Keywords

Th17pMHC I complexesCD8+ CTLCCL2/20Antitumor immunity

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Manjunatha Ankathatti Munegowda
    • 1
    • 2
  • Yulin Deng
    • 1
    • 2
  • Sean J. Mulligan
    • 3
  • Jim Xiang
    • 1
    • 2
  1. 1.Research Unit, Saskatchewan Cancer Agency, Department of OncologyUniversity of SaskatchewanSaskatoonCanada
  2. 2.Research Unit, Saskatchewan Cancer Agency, Department of Immunology PathologyUniversity of SaskatchewanSaskatoonCanada
  3. 3.Research Unit, Saskatchewan Cancer Agency, Department of PhysiologyUniversity of SaskatchewanSaskatoonCanada