The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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Caronni, N., La Terza, F., Vittoria, F.M, Barbiera, G. et al. Nature. 623, pages 415–422 (2023).
doi: doi.org/10.1038/s41586-023-06685-2.
Summary of the findings
Summary of the findingsPancreatic ductal adenocarcinoma (PDAC) is a deadly disease with few therapeutic options. Tissue damage and the ensuing inflammatory responses are known to favor pancreatic tumorigenesis by cooperating with oncogenic mutations in epithelial cells. In this article, the authors leverage advanced genomic techniques to elucidate pathogenic programs underlying tumor-promoting inflammation in PDAC. They identified a population of tumor- associated macrophages (TAMs) expressing the cytokine interleukin-1β (IL-1β) – hence termed IL-1β+ TAMs – able to stimulate inflammatory reprogramming and consequently increase the pathogenic potential of tumor cells. IL-1β+ TAMs originate from PDAC-infiltrating monocytes upon exposure to the lipid mediator prostaglandin E2 (PGE2) in the tumor microenvironment. A key finding of the study is the physical proximity between IL-1β+ TAMs and a subset of tumor cells expressing an IL-1β response signature (T1RS) in PDAC patients, highlighting a local interaction between these cells that foster tumor growth. The authors also showed that inflammatory reprogramming of epithelial cells is an early event in pancreatic tumorigenesis upon oncogenic mutations and tissue damage.
Future impact
This work identifies the PGE2-IL-1β axis as a physiological response to injury whose cooptation in cancer may support disease initiation or progression. Targeting the PGE2-IL-1β could prove beneficial as combinatorial immunotherapy for patients with advanced PDAC, as well as preventive treatment for individuals at risk.
