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

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Pancreatic ductal adenocarcinoma (PDAC) frequently recurs after surgical resection.
• Identifying the immune microenvironment's role in PDAC recurrence is crucial for improving patient prognosis.

Purpose of the Study:

• To investigate the spatially organized immune determinants associated with different pancreatic ductal adenocarcinoma recurrence sites.
• To correlate immune profiles with recurrence patterns and patient outcomes.

Main Methods:

• Classification of 284 PDACs into recurrence groups (liver, lung, local, peritoneal, no-recurrence).
• Spatial compartment identification (tumor cells, leukocytes, stromal cells) using fluorescent imaging.
• Transcriptomic and proteomic analysis of immune pathway targets, integrated with next-generation sequencing data.
• Immunophenotypic analysis by multiplex immunofluorescence in a validation cohort.

Main Results:

• No-recurrent PDACs exhibit high immunogenicity and adaptive immune responses.
• Liver/peritoneal recurrences are associated with low immunogenicity, stemness, and innate immune responses.
• Local/lung recurrences show interferon-gamma signaling and mixed immune responses, with distinct immune cell populations.
• No significant genetic differences were observed, except for RNF43 mutations in the no-recurrence group.

Conclusions:

• Distinct inflammatory and stromal responses correlate with PDAC recurrence patterns and patient outcomes.
• Findings may inform personalized adjuvant/neoadjuvant therapies and surveillance strategies for PDAC.
• The study highlights the potential of immunotherapeutic modalities based on immune microenvironment characteristics.