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Tumour immunology

Innate immune activation enhances tumour immunotherapy

Nature Reviews Immunology volume 7, pages 662–663 (2007)Cite this article

To investigate whether, in addition to removal of cytokine sinks and regulatory T cells, other mechanisms are operational in the effect of TBI, the authors assessed the impact of TBI and ACT in mice deficient for both recombination-activating gene 2 (RAG2) and the common cytokine receptor g-chain (Rag2−/−Il2rg−/− mice), in which neither of these mechanisms is effective. Adoptive transfer of 105 T-cell receptor (TCR)-transgenic CD8+ T cells reactive against the tumour-associated antigen glycoprotein 100 (gp100), together with a recombinant fowlpox virus encoding gp100 and interleukin-2 (IL-2), was more effective in the eradication of large B16F10 tumours in irradiated versus non-irradiated mice. Tumour eradication was not associated with an increase in the absolute numbers of transferred T cells. However, 5 days after ACT, recovered T cells from irradiated mice produced higher amounts of pro-inflammatory cytokines compared with T cells from non-irradiated mice.

So, how does TBI lead to enhanced function of transferred T cells? In irradiated mice, the authors observed an increase in the absolute number of activated dendritic cells (DCs) that produced more IL-12p70, suggesting that they were more highly activated than DCs from non-irradiated mice. As TBI is known to alter gut homeostasis, the authors next looked at whether this disruption was contributing to the enhanced DC activation state. Translocated gut bacteria were detected in the mesenteric lymph nodes and systemic circulation of mice treated with TBI. In addition, lipopolysaccharide (LPS) — a component of the cell wall of Gram-negative bacteria — and elevated levels of pro-inflammatory cytokines were detected in the sera of irradiated mice.

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References

ORIGINAL RESEARCH PAPER

  1. Paulos, C. M. et al. Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling. J. Clin. Invest. 117, 2197–2204 (2007)

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FURTHER READING

  1. Gattinoni, L. Powell, D. J. Jr, Rosenberg, S. A. & Restifo, N. P. Adoptive immunotherapy for cancer: building on success. Nature Rev. Immunol. 6, 383–393 (2006)

    Article  CAS  Google Scholar 

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Authors
  1. Elaine Bell
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Bell, E. Innate immune activation enhances tumour immunotherapy. Nat Rev Immunol 7, 662–663 (2007). https://doi.org/10.1038/nri2158

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