The tumour immune microenvironment and its response to exercise during treatment for oesophagogastric cancer
Casey, P. Tarazi, M. Powell, A. Baker, Alexander Ashton, Garry Valpione, Sara Redfern, J. McGrath, S. Sultan, J.
Casey, P.
Tarazi, M.
Powell, A.
Baker, Alexander
Ashton, Garry
Valpione, Sara
Redfern, J.
McGrath, S.
Sultan, J.
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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.
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Date
2024
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Collections
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Article
Citation
Casey P, Tarazi M, Powell A, Baker A, Ashton G, Valpione S, et al. The tumour immune microenvironment and its response to exercise during treatment for Oesophagogastric cancer. BRITISH JOURNAL OF SURGERY. 2024 MAR 18;111. PubMed PMID: WOS:001221532100124. English.