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

Abstract

immune signatures of immunotherapy-specific of cell subsets utilising mass cytometry with 38 markers. Results and discussions PD-L1 blockade induced the expansion of highly specific tumor-infiltrating CD4 and CD8 T cells, displaying both activating (ICOS) and inhibitory (PD-1, LAG-3) molecules. Expansion of these therapy-induced T cell subsets was observed three days after treatment and significantly expanded in time leading to tumour delay. By targeting the activating and inhibiting molecules on the T cells by agonistic and blocking antibodies, respectively, we were able to further restore the T cell dysfunction and thereby improving the therapeutic benefit of single immunotherapy. Conclusion Thus, high-dimensional profiling is a powerful means for rational designing combinatorial T-cell based immunotherapies. PO-363ABSTRACT WITHDRAWN Introduction Several preclinical studies have shown that exercise can reduce the tumour growth across a range of tumour models.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 epinephrinedependent mobilisation and IL-6-driven activation of cytotoxic cells. In line with this, exercise markedly increased intratumoral immune cell infiltration, thus promoting an immunestimulatory intratumoral environment. Based on these original findings, we hypothesised that exercise may enhance the effect of immune checkpoint blockade treatment given the exercisedependent increased intratumoral immune cell infiltration. Material and methods We 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 aPD-L1 antibodies (100 mg per mouse three times per week starting on day 4 after tumour cell injection). Results and discussions First, 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 aPD-L1 antibody treatment. In this setup, wheel running had an overall suppressive effect (p=0.01, 2-way ANOVA). Post hoc analysis showed that aPD-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. PO-364 EFFECT OF EXERCISE AND IMMUNOTHERAPY ON TUMOUR IMMUNOGENICITY AND GROWTH

Is There a Role for Exercise When Treating Patients with Cancer with Immune Checkpoint Inhibitors? A Scoping Review

“…Within the ten remaining studies [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], the type, intensity, duration and level of supervision of the exercise intervention varied, with two studies also administering it alongside additional non-pharmacological interventions [ 36 , 39 ]. Aerobic-only exercise interventions were delivered in the mouse studies, of which three used a supervised approach [ 33 , 34 , 35 ] and four used an unsupervised approach [ 36 , 37 , 40 , 41 ]. Exercise interventions were less prescribed in the clinical studies, each reporting a mixture of aerobic and/or resistance exercise which was supervised and/or unsupervised [ 38 , 39 , 42 ].…”

“…Melanoma, breast cancer and lung cancer were the most common cancer types specified within the inclusion criteria of the ten studies. Two studies, using preclinical mouse models, delivered the exercise and ICI interventions sequentially [ 37 , 40 ]. The exercise intervention was conducted in the pre-implant setting (i.e., before tumour inoculation), whilst the ICI intervention was delivered in the post-implant setting (i.e., after tumour inoculation).…”

“…Table 3 includes findings from studies addressing the impact of exercise on oncological responses to ICIs (n = 7), all of which were preclinical studies in mouse models of cancer which administered an aerobic-only exercise intervention [ 33 , 34 , 35 , 36 , 37 , 40 , 41 ]. The most common outcome measures related to tumour growth.…”

“…Although their study design permitted, the remaining studies (n = 3) did not provide a direct comparison of oncological responses to the combined approach versus the ICI intervention alone [ 36 , 37 , 41 ]. Instead, the exercise intervention alone [ 36 , 37 ] and a no intervention control [ 41 ] were used as the predominant comparator. No significant differences in oncological outcomes were identified in these studies.…”

“…Table 5 includes the outcome measures and relevant findings from the studies addressing potential biological mechanisms (n = 7). All were preclinical studies in mouse models and were the same seven studies that addressed the impact of aerobic exercise on oncological outcomes when combined with ICI treatment [ 33 , 34 , 35 , 36 , 37 , 40 , 41 ].…”