Voluntary wheel running can lead to modulation of immune checkpoint molecule expression

Autor: Nicole Unterrainer, Mie Marienhof Staffeldt, Pernille Hojman, Rikke Stagaard, Bente Klarlund Pedersen, Marie Lund Bay, Julie Gehl, Tim Schauer, Katrine Seide Pedersen, Jesper Christensen
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Bay, M L, Unterrainer, N, Stagaard, R, Pedersen, K S, Schauer, T, Staffeldt, M M, Christensen, J F, Hojman, P, Pedersen, B K & Gehl, J 2020, ' Voluntary wheel running can lead to modulation of immune checkpoint molecule expression ', Acta Oncologica, vol. 59, no. 12, pp. 1447-1454 . https://doi.org/10.1080/0284186X.2020.1817550
DOI: 10.1080/0284186X.2020.1817550
Popis: BackgroundExercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy.Material and methodsThe experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors.ResultsWheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels.ConclusionB16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.
Databáze: OpenAIRE