The tumour immune microenvironment and its response to exercise during treatment for oesophagogastric cancer

Abstract

Introduction: Pre-clinical studies suggest that exercise during cancer treatment may enhance tumour regression and promote an anti-tumorigenic immune microenvironment. Considering the evolution of immunotherapy in oesophagogastric cancer, further understanding of the host-tumour immune response to exercise therapy is of significant interest. Methods: Using multiplex immunofluorescence, resection specimens of 30 patients with oesophageal adenocarcinoma were labelled for CD3, CD4, CD8, PD-1, PD-L1, FOXP3, CD68, and PanCK to characterise tumour and peri-tumoral immune infiltrate. All patients received the same neoadjuvant chemotherapy prior to oesophagectomy. 14 patients who engaged with a structured prehabilitation exercise program (mixed aerobic and resistance training twice-weekly) were case-matched with 16 control patients who did not. Results: The prehabilitation group had a significant increase (per mm2 ) in cytotoxic T-cells (99.4 vs 13.8, p=0.003). There was also a significant increase in immune suppressive macrophages, exhausted T-helper and cytotoxic T-cells. The only significant change in the peritumoural sections was an increase in exhausted CD8 cytotoxic-T cells in the prehabilitation group (3.3 vs 1.4, p=0.043). There was no difference in the number of Treg or T-helper cells within, or around the tumour sections. Conclusions: This study is the ‘first-in-man’ to show that exercise prehabilitation during chemotherapy impacts on the tumour immune microenvironment in patients with oesophageal adenocarcinoma. Exercise results in an increased abundance of both anti-tumorigenic and immunosuppressive cell types. These finding warrant further investigation, especially in the context of modern immunotherapy treatments, to understand the clinical impact that exercise oncology has on tumour regression.