PO-364 Effect of exercise and immunotherapy on tumour immunogenicity and growth

Abstract

IntroductionSeveral preclinical studies have shown that exercise can reduce the tumour growth across a range of tumour models. We recently demonstrated that this exercise-dependent suppression of tumour growth was due to an epinephrine-dependent mobilisation and IL-6-driven activation of cytotoxic cells. In line with this, exercise markedly increased intratumoral immune cell infiltration, thus promoting an immune-stimulatory intratumoral environment. Based on these original findings, we hypothesised that exercise may enhance the effect of immune checkpoint blockade treatment given the exercise-dependent increased intratumoral immune cell infiltration.Material and methodsWe used C57Black/C mice randomised to cages with or without running wheels (EX). After 4 weeks of running (with a running distance ranging from 1.8 km to 5.4 km per mice per day), the mice were inoculated with B16 melanoma cancer cells. In addition, a subset of mice was treated with αPD-L1 antibodies (100 µg per mouse three times per week starting on day 4 after tumour cell injection).Results and discussionsFirst, we observed that voluntary wheel running increased intratumoral expression of the immune checkpoint molecules, PD-L1, B7.1 and B7.2. In parallel, voluntary wheel running increased intratumoral infiltration of cytotoxic NK and T cells, and thus intratumoral expression of the receptors, PD-1 and CD28. Next, we tested the combination therapy of exercise and αPD-L1 antibody treatment. In this setup, wheel running had an overall suppressive effect (p=0.01, 2-way ANOVA). Post hoc analysis showed that αPD-L1 +EX reduced tumour growth by 82.6%, while EX alone reduced tumour growth by 72% with no significant difference between the two interventions. qPCR analysis of these tumours revealed that combination therapy further increased the expression of immune cell markers and immune check point molecules.ConclusionIn conclusion, our results show that exercise increases the expression of immune checkpoint markers and therefore, could be a good combination partner for immune checkpoint blockade treatment. However, more studies are needed to show an effect of this combination therapy on tumour growth.