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A novel target for combination immunotherapy in pancreatic cancer: IL-1β mediates immunosuppression in the tumour microenvironment

British Journal of Cancer volume 124, pages 1754–1756 (2021)Cite this article

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Summary

Immune checkpoint blockade (ICB) has demonstrated efficacy in multiple cancers, offering the potential of long-term disease control not achievable with cytotoxic or targeted therapies. However, the field has not yet achieved the crucial next steps — the expansion of the response rate and achievement of clinical efficacy in so-called “cold tumours”. Mechanistic studies of tumour-type specific immunosuppressive pathways can reveal underlying biological hurdles to immunotherapy and offer new therapeutic insights. Our finding that tumour-derived IL-1β mediates immunosuppression in pancreatic cancer has precipitated a new clinical trial.

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Fig. 1: Tumour-cell-derived production of IL-1β is dependent on TLR4 signalling, probably activated by microbial ligands in the tumour microenvironment.

References

  1. Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).

    Article  CAS  Google Scholar 

  2. Mantovani, A., Barajon, I. & Garlanda, C. IL-1 and IL-1 regulatory pathways in cancer progression and therapy. Immunol. Rev. 281, 57–61 (2018).

    Article  CAS  Google Scholar 

  3. Tu, S., Bhagat, G., Cui, G., Takaishi, S., Kurt-Jones, E.A., Rickman, B. et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14, 408–419 (2008).

    Article  CAS  Google Scholar 

  4. Carmi, Y., Dotan, S., Rider, P., Kaplanov, I., White, M.R., Baron, R. et al. The role of IL-1beta in the early tumor cell-induced angiogenic response. J. Immunol. 190, 3500–3509 (2013).

    Article  CAS  Google Scholar 

  5. Bunt, S. K., Sinha, P., Clements, V. K., Leips, J. & Ostrand-Rosenberg, S. Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J. Immunol. 176, 284–290 (2006).

    Article  CAS  Google Scholar 

  6. Ridker, P. M., MacFadyen, J.G., Thuren, T., Everett, B.M., Libby, P., Glynn, R.J. et al. Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: Exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390, 1833–1842 (2017).

    Article  CAS  Google Scholar 

  7. Das, S., Shapiro, B., Vucic, E. A., Vogt, S. & Bar-Sagi, D. Tumor cell-derived IL1beta promotes desmoplasia and immune suppression in pancreatic cancer. Cancer Res. 80, 1088–1101 (2020).

    Article  CAS  Google Scholar 

  8. Biffi, G. & Tuveson, D. A. Diversity and biology of cancer-associated fibroblasts. Physiol. Rev. 101, 147–176 (2021).

    Article  Google Scholar 

  9. Riquelme, E., Zhang, Y., Zhang, L., Montiel, M., Zoltan, M., Dong, W. et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178, 795–806.e712 (2019).

    Article  CAS  Google Scholar 

  10. Winograd, R., Byrne, K.T., Evans, R.A., Odorizzi, P.M., Meyer, A.R., Bajor, D.L. et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma. Cancer Immunol. Res. 3, 399–411 (2015).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Oncology, NYU Langone Health, New York, NY, USA

    Rafael Winograd

  2. Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA

    Rafael Winograd & Diane M. Simeone

  3. Department of Surgery, NYU Langone Health, New York, NY, USA

    Diane M. Simeone

  4. Department of Pathology, NYU Langone Health, New York, NY, USA

    Diane M. Simeone

  5. Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, USA

    Dafna Bar-Sagi

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  1. Rafael Winograd
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  2. Diane M. Simeone
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  3. Dafna Bar-Sagi
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R.W., D.S., and D.B.-S. wrote and edited the paper.

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Correspondence to Dafna Bar-Sagi.

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The authors declare no competing interests.

Funding information

This work was supported by NIH/NCI grants CA210263 (D. Bar-Sagi) and CA131045 (D.M. Simeone), Lustgarten Foundation Pancreatic Cancer Convergence Dream Team grant SU2C-AACR-DT14-14 (D. Bar-Sagi), and PanCAN Precision Promise (D.M. Simeone). Stand Up To Cancer is a programme of the Entertainment Industry Foundation administered by the American Association for Cancer Research.

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Winograd, R., Simeone, D.M. & Bar-Sagi, D. A novel target for combination immunotherapy in pancreatic cancer: IL-1β mediates immunosuppression in the tumour microenvironment. Br J Cancer 124, 1754–1756 (2021). https://doi.org/10.1038/s41416-021-01303-2

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