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  • Open Access

Unleashing the power of anti-tumor CD4+ T cells: novel insights into the curative mechanisms of chemoimmunotherapy for cancer

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  • 1
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P18

https://doi.org/10.1186/2051-1426-3-S2-P18

Published: 4 November 2015

Keywords

  • Metabolic Profile
  • Interferon Gamma
  • Adoptive Transfer
  • Tumor Rejection
  • Rational Combination

Background

CD4+ T cells are critical mediators of anti-tumor immunity and orchestrate a broad range of immune responses against cancer. Previous studies from our lab and others have demonstrated that, adoptive transfer of tumor specific CD4+ T cells to lymphopenic hosts led to eradication of established tumors in mice models. Accumulating evidence from preclinical and clinical studies also suggest that CD4+ T cells in combination with chemotherapy can control tumor progression and recurrence. However, the molecular and cellular mechanisms by which tumor reactive CD4+ T cells eliminate a wide variety of tumors are not completely understood.

Methods

In this project, we set out to study the mechanisms underlying the therapeutic effect of chemo-immunotherapy in the form of cyclophosphamide (CTX) and tumor specific CD4+ T cells. Recent studies have revealed that combined effect of Th-1 cytokines, IFN-γ and TNF, drive both murine and human cancer cells in to senescence. In the present study we wanted to examine the specific roles of IFN-γ and TNF-α in the setting of chemoimmunotherapy and the contribution of other immune cells in the tumor microenvironment to tumor rejection beside the donor CD4+ T cells.

Results

In a mouse model of colorectal cancer, we found that host-derived interferon gamma (IFN-γ) and expression of IFN-γR are critical components of CD4+T cell-mediated tumor rejection, whereas depletion of NK cells and macrophages separately did not compromise the therapeutic effect of the CTX and CD4+T cells regimen. In addition, IFN-γ appeared to drive tumor senescence and apoptosis in vivo, leading to a curative outcome. Furthermore, we analyzed the global metabolic profiling of tumor tissues at different time points before and after chemoimmunotherapy.

Conclusions

Our data suggests that CD4+T cells reprogram the metabolic profiling in tumor, tipping the balance towards progressive tumor regression. These findings may provide new insights into mechanisms of tumor rejection by CD4+ T cells, and may help develop more effective anti-tumor strategies based on a rational combination of chemotherapy and anti-tumor CD4+ T cells.

Authors’ Affiliations

(1)
Georgia Regents University, Augusta, USA

Copyright

© Habtetsion and Zhou 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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