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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Hansen, N. et al. JITC. 12: e009523. (2024).
doi: 10.1136/jitc-2024-009523.
Summary of the findings
Summary of the findingsPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer characterized by an immune-suppressive tumor microenvironment. This study investigates the role of the IL-1 receptor accessory protein (IL1RAP), which is highly expressed on both tumor cells and stroma, and correlates with poor prognosis. Targeting IL1RAP with the antibody nadunolimab significantly inhibited tumor growth in xenograft models, with effects dependent on cancer-associated fibroblasts (CAFs). Specifically, inhibition of IL1RAP on CAFs reduced the secretion of critical chemokines preventing the migration of neutrophils and monocytes, immune cells that contribute to the tumor’s immune-suppressive environment. Notably, nadunolimab treatment not only suppressed neutrophil migration but significantly reduced their viability. Furthermore, nadunolimab enhanced monocyte-mediated antibody-dependent cellular cytotoxicity against PDAC cells. In a clinical trial, high IL1RAP expression was associated with longer progression-free survival in late-stage metastatic PDAC patients treated with nadunolimab, validating IL1RAP as a promising therapeutic target in PDAC. These findings underscore the pivotal role of IL1RAP on CAFs in immune suppression within PDAC.
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Future impact
Targeting IL1RAP could disrupt CAF-mediated immune suppression, particularly the recruitment of neutrophils, offering a promising new therapeutic opportunity for PDAC patients.
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