A pioneering pilot study conducted collaboratively by the University of Surrey and the Royal Surrey NHS Foundation Trust has uncovered compelling evidence that exercise during chemotherapy and prior to surgical intervention may significantly enhance the immune system’s ability to infiltrate and combat oesophageal adenocarcinoma tumors. This innovative research forms the basis for a larger clinical trial named OPTIMUS, spearheaded by Professor Adam Frampton, a Consultant General Surgeon and scientist. The implications of this work could profoundly influence future oncological treatment protocols by integrating structured physical activity to augment therapeutic outcomes at a mechanistic level.
The study, detailed in the forthcoming issue of the Journal of Sport and Health Sciences, represents the first randomized controlled trial in humans to investigate the effects of prehabilitation—exercise performed during chemotherapy—on the tumor immune microenvironment specifically in oesophageal adenocarcinoma. This form of cancer, originating in the glandular cells of the oesophagus, remains a formidable clinical challenge, often presenting poor prognoses due to its aggressive nature and late diagnosis. The trial enrolled 22 patients from the Royal Surrey NHS Foundation Trust, a renowned cancer center, with eleven participants engaging in a 16-week structured exercise regimen, while eleven acted as controls without intervention.
The exercise protocol implemented consisted of two supervised sessions weekly during the chemotherapy phase, approximately spanning eight weeks, followed by a progressive exercise phase leading up to surgical resection. This regimen was meticulously designed to improve patients’ aerobic capacity and overall fitness, parameters believed to influence immune competence. Post-surgery, researchers harvested tumor specimens for in-depth immunological and genomic analyses. Utilizing multispectral immunohistochemistry, they quantified tumor-infiltrating immune cells, while gene expression profiling was conducted with NanoString technology, a high-throughput, precise method for measuring mRNA levels within tumor tissues.
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Dr. Nicola Annels, co-senior author and cancer immunologist, highlighted the novelty of the findings, noting that this is the first trial to demonstrate a tangible modulation of the tumor microenvironment through exercise during chemotherapy. Specifically, tumors from patients undergoing the prehabilitation program exhibited a notable increase in cytotoxic immune populations, including CD8+ T cells and natural killer (NK) cells, which are critical effectors in antitumor immunity. These immune cells facilitate targeted destruction of cancer cells and have been correlated with improved responses to oncological treatments, implying that exercise may prime the tumor milieu for enhanced immunological assault.
Despite the promising results, Dr. Annels emphasized the exploratory nature of the study and the necessity for further research to consolidate these observations. Previous investigations, predominantly conducted in animal models, have suggested exercise-mediated enhancement of immune surveillance and suppression of tumor growth. However, analogous human studies, largely focused on prostate and colorectal cancers, failed to observe an increase in tumor-infiltrating immune cells, underscoring the complexity of translating preclinical findings into clinical practice.
The involvement of Dr. David Bartlett, co-first author and exercise physiologist, further elucidates the relationship between aerobic fitness and immune response. His team discovered a positive correlation between improvements in patients’ cardiorespiratory fitness and the density of immune cells within their tumors. Notably, they identified mature tertiary lymphoid structures—organized immune cell aggregates that function as local immune hubs—within tumor tissues from fitter individuals. The presence of these structures associates with heightened antitumor responses and better clinical outcomes, suggesting that exercise may facilitate the formation or maturation of these critical immune architectures.
The OPTIMUS trial, currently expanding with a target enrollment of 50 subjects, aims to robustly assess the impact of prehabilitation on clinical endpoints. Participants are randomized to either the previously tested moderate intensity exercise group or a novel higher intensity protocol hypothesized to elicit superior immunomodulatory effects. Preliminary data from seven patients already enrolled in OPTIMUS have revealed cases of complete tumor regression where no residual tumor was detected during operative examination—a rare phenomenon occurring in only about 6% of such patients under standard care. This early indication, while anecdotal, alludes to the transformative potential of exercise interventions in neoadjuvant cancer therapy.
Clinically, patients involved in the trial have exhibited improved physical resilience, translating into better perioperative outcomes and enhanced recovery trajectories. Mr. Charles Rayner, co-first author and specialist surgeon, remarked on the increased fitness levels allowing patients to withstand surgical stress and recuperation more effectively. This functional improvement is pivotal given that surgical morbidity and mortality remain significant concerns in oesophageal cancer management.
Senior author Mr. Nima Abbassi-Ghadi underscored the real-world impact of these findings, affirming that patient feedback overwhelmingly reflects augmented well-being and capability through preoperative exercise engagement. Remarkably, some participants who might otherwise have been ineligible for curative surgery due to frailty have attained sufficient fitness levels to undergo successful resections, highlighting the pragmatic implications of integrating structured exercise into therapeutic pathways.
Patient testimonies provide a poignant narrative complementing the scientific data. One participant described the OPTIMUS program as a vital source of agency and support amid the turmoil of cancer treatment. The emotional intelligence and personalized care offered by the research team were as critical as the physical conditioning itself, illustrating the holistic benefits—both psychological and physiological—that exercise prehabilitation confers during oncological care.
Researchers encourage eligible patients receiving treatment at Royal Surrey Cancer Centre to inquire about participation in the ongoing trial. Direct contact can be made via Dr. Bartlett and Dr. Annels, endorsing a collaborative and accessible research environment focused on transforming cancer treatment paradigms.
This study was generously funded by the World Cancer Research Fund as part of their International grant program, reflecting a global commitment to innovative cancer research that bridges basic science and clinical application. The emerging evidence from this research promises to redefine the role of exercise as a potent adjunct in cancer therapy, fostering a multidisciplinary approach to improving patient survival and quality of life.
Subject of Research: Effects of structured exercise prehabilitation during neoadjuvant chemotherapy on tumor-infiltrating immune cells in oesophageal adenocarcinoma
Article Title: Prehabilitation during neoadjuvant chemotherapy results in an enhanced immune response in oesophageal adenocarcinoma tumours: a randomised controlled trial
News Publication Date: 9-Jun-2025
Web References:
DOI link
References:
Available upon embargo lift through [email protected]
Image Credits:
An image of Dr. Nicola Annels and Dr. David Bartlett available via contact with [email protected]
Keywords: Cancer immunology, Esophageal cancer, Cancer cells, Cancer research, Oncology, Physical exercise
Tags: clinical trial on exercise benefitsexercise during chemotherapyimmune response to cancer treatmentinnovative cancer treatment protocolsoesophageal adenocarcinoma researchOPTIMUS trial findingsphysical activity and oncologyprehabilitation in cancer careRoyal Surrey NHS Foundation Trust collaborationstructured exercise regimen for cancer patientstumor immune microenvironment studyUniversity of Surrey cancer research
