Cancer Immunology, Immunotherapy

, Volume 65, Issue 3, pp 247–259 | Cite as

Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic

  • Kinga Majchrzak
  • Michelle H. Nelson
  • Stefanie R. Bailey
  • Jacob S. Bowers
  • Xue-Zhong Yu
  • Mark P. Rubinstein
  • Richard A. Himes
  • Chrystal M. Paulos
Review

Abstract

Cancer immunotherapy is one the most effective approaches for treating patients with tumors, as it bolsters the generation and persistence of memory T cells. In preclinical work, it has been reported that adoptively transferred CD4+ and CD8+ lymphocytes that secrete IL-17A (i.e., Th17 and Tc17 cells) regress tumors to a greater extent than IFN-γ+Th1 or Tc1 cells in vivo. Herein, we review the mechanisms underlying how infused Th17 and Tc17 cells regress established malignancies in clinically relevant mouse models of cancer. We also discuss how unique signaling cues—such as co-stimulatory molecules (ICOS and 41BB), cytokines (IL-12 and IL-23) or pharmaceutical reagents (Akt inhibitors, etc.)—can be exploited to bolster the therapeutic potential of IL-17+ lymphocytes with an emphasis on using this knowledge to improve next-generation clinical trials for patients with cancer.

Keywords

Th17 Tc17 Cancer Immunotherapy ACT 

Abbreviations

ACT

Adoptive cell therapy

CAR

Chimeric antigen receptor

ICOS

Inducible co-stimulator

IRF4

Interferon regulatory factor 4

ROR

Retinoic acid-related orphan receptor

RUNX

Runt-related transcription factor

Tc17

IL-17-producing CD8 cytotoxic T cell

TCR

T cell receptor

Th17

IL-17-producing CD4 helper T cell

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Kinga Majchrzak
    • 1
    • 2
    • 3
  • Michelle H. Nelson
    • 1
    • 2
  • Stefanie R. Bailey
    • 1
    • 2
  • Jacob S. Bowers
    • 1
    • 2
  • Xue-Zhong Yu
    • 1
  • Mark P. Rubinstein
    • 2
  • Richard A. Himes
    • 4
  • Chrystal M. Paulos
    • 1
    • 2
  1. 1.Department of Microbiology and Immunology, Hollings Cancer CenterMedical University of South CarolinaCharlestonUSA
  2. 2.Department of SurgeryMedical University of South CarolinaCharlestonUSA
  3. 3.Department of Physiological Sciences, Faculty of Veterinary MedicineWarsaw University of Life Sciences - WULSWarsawPoland
  4. 4.Department of Chemistry and BiochemistryCollege of CharlestonCharlestonUSA

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