Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice

Manon Gouez (1) , Amélie Rébillard (2) , Amandine Thomas (3) , Sabine Beaumel (4) , Eva-Laure Matera (4) , Etienne Gouraud (3) , Luz Orfila (2) , Brice Martin (2) , Olivia Pérol (1, 5) , Cedric Chaveroux (6, 4) , Erica N. Chirico (7) , Charles Dumontet (6, 4) , Béatrice Fervers (4, 1) , Vincent Pialoux (3)

1 Centre Léon Bérard [Lyon]
2 M2S - Laboratoire Mouvement Sport Santé
3 LIBM - Laboratoire Interuniversitaire de Biologie de la Motricité
4 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
5 Inserm U1296 - Unité Ad Hoc INSERM 000008 "Radiations : Défense, Santé, Environnement" [Lyon]
6 HCL - Hospices Civils de Lyon
7 CMSRU - Cooper Medical School of Rowan University [Camden]

Acute exercise induces transient modifications in the tumor microenvironment and has been linked to reduced tumor growth along with increased infiltration of immune cells within the tumor in mouse models. In this study, we aimed to evaluate the impact of acute exercise before treatment administration on tumor growth in a mice model of MC38 colorectal cancer receiving an immune checkpoint inhibitor (ICI) and chemotherapy. Six-week-old mice injected with colorectal cancer cells (MC38) were randomized in 4 groups: control (CTRL), immuno-chemotherapy (TRT), exercise (EXE) and combined intervention (TRT/EXE). Both TRT and TRT-EXE received ICI: anti-PD1-1 (1 injection/week) and capecitabine + oxaliplatin (5 times a week) for 1 week (experimentation 1), 3 weeks (experimentation 2). TRT-EXE and EXE groups were submitted to 50 minutes of treadmill exercise before each treatment administration. Over the protocol duration, tumor size has been monitored daily. Tumor growth and microenvironment parameters were measured after the intervention on Day 7 (D7) and Day 16 (D16). From day 4 to day 7, tumor volumes decreased in the EXE/TRT group while remaining stable in the TRT group (p=0.0213). From day 7 until day 16 tumor volume decreased with no significant difference between TRT and TRT/EXE. At D7 the TRT/EXE group exhibited a higher total infiltrate T cell (p=0.0118) and CD8+ cytotoxic T cell (p=0.0031). At D16, tumor marker of apoptosis, vascular integrity and inflammation were not significantly different between TRT and TRT/EXE. Our main result was that acute exercise before immuno-chemotherapy administration significantly decreased early-phase tumor growth (D0 to D4). Additionally, exercise led to immune cell infiltration changes during the first week after exercise, while no significant molecular alterations in the tumor were observed 3 weeks after exercise.

Mots clés: colorectal cancer; acute exercise; immune check point inhibitor; immune cell; cancer immunotherapy

Domaines: Cancer; Immunothérapie; Hépatologie et Gastroentérologie; Pharmacologie

Manon Gouez, Amélie Rébillard, Amandine Thomas, Sabine Beaumel, Eva-Laure Matera, et al.. Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice. Frontiers in Immunology, 2024, 15, pp.1368550. ⟨10.3389/fimmu.2024.1368550⟩. ⟨hal-04479752⟩