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


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.


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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.

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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).

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