Spatially restricted tumour-associated and host-associated immune drivers correlate with the recurrence sites of pancreatic cancer.

Most patients with pancreatic ductal adenocarcinoma (PDAC) will experience recurrence after resection. Here, we investigate spatially organised immune determinants of PDAC recurrence. PDACs (n=284; discovery cohort) were classified according to recurrence site as liver (n=93/33%), lung (n=49/17%), local (n=31/11%), peritoneal (n=38/13%) and no-recurrence (n=73/26%). Spatial compartments were identified by fluorescent imaging as: pancytokeratin (PanCK) No-recurrent PDACs show high immunogenicity, adaptive immune responses and are rich in pro-inflammatory chemokines, granzyme B and alpha-smooth muscle actin Our findings demonstrate distinct inflammatory/stromal responses in each recurrence group, which might affect dissemination patterns and patient outcomes. These findings may help to inform personalised adjuvant/neoadjuvant and surveillance strategies in PDAC, including immunotherapeutic modalities.

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Competing interests: None declared.