Investigating immunological, transcriptomic and metabolomic signatures and their association with pneumonia after upper gastrointestinal cancer surgery

Abstract Upper gastrointestinal (UGI) cancer is an increasing global health problem. Surgical resection is the primary curative intervention yet is associated with high-risk of post-operative pneumonia. This study aims to characterise how UGI cancer impacts biological ageing, and evaluate their association with post-operative pneumonia. A single-centre observational pilot study recruiting UGI cancer patients prior to elective oesophagectomy surgery and twenty age- and sex-matched healthy controls. Reduced frequencies of naïve CD8 T cells and expansion of CD28 − CD57 + CD8 senescent T cells were observed pre-operatively and persisted post-operatively in UGI patients, compared to healthy controls. Increased inflammatory cytokines and transcriptomic and metabolomic signatures associated with reduced autophagy, metabolic programming and microbiome dysbiosis were also observed. Post-operative pneumonia developed in 65% (n = 13) of the UGI cohort. Despite being chronologically younger, patients with pneumonia had significantly raised pre-operative inflammatory profile, identified by inflammatory cytokines, transcriptomic and metabolomic signatures. This exploratory pilot study identifies evidence of enhanced immune ageing in UGI surgical patients at pre-operative baseline, which persists post-operatively. Pre-operative inflammatory profiles potentially contribute to the susceptibility of post-operative pneumonia. While validation in larger cohorts is necessary, these findings are hypothesis-generating and provide early insight into potential immunological targets to mitigate post-operative risk.