Objective: Treatment with immunotherapy has positively changed the long-term outlook of many patients with advanced melanoma; however, fatigue is a common and debilitating side effect.,Evidence indicates exercise can improve treatment-related fatigue for patients receiving chemotherapy and radiotherapy.,However, currently little is known about exercise behaviors and preferences of patients receiving immunotherapy.,This project aimed to describe self-reported levels of fatigue related to immunotherapy; patient perspectives of exercise behaviors; and barriers and facilitators to engagement in exercise for patients receiving, or recently completed immunotherapy for unresectable stage III and stage IV melanoma.,Method: A cross-sectional purpose-built survey was distributed to members of the Melanoma Patients Australia closed Facebook group via an online survey platform.,The survey remained active for 1 month, with 3 posts during this time inviting members to participate.,Results: A total of 55 responses were collected.,Just over half the participants (n = 31; 56%) described exercising while receiving immunotherapy, with walking as the most common activity (n = 24; 77%).,Participants described a range of physical and emotional benefits of exercise, the most predominant being fatigue reduction.,Barriers to exercise also included fatigue and competing physical demands at home or work.,Patient understanding of what constitutes exercise appeared to differ from clinical classifications.,Conclusions: Results from this study indicate that patients are engaging in exercise while receiving immunotherapy, with the intent of mediating treatment-related fatigue.,Identification of preferred exercise activities and barriers will assist in developing tailored exercise interventions for this cohort.
Tumor cells evade the immune surveillance by up-regulating surface expression of PD-L1, which interacts with PD-1 on T cells to elicit the immune checkpoint response1,2.,Anti-PD-1 antibodies have shown remarkable promise in treating tumors, including metastatic melanoma2-4.,However, patient response rate is low4,5.,A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy.,Here we report that metastatic melanoma releases a high level of extracellular vesicles (EVs), mostly in the form of exosomes, that carry PD-L1 on their surface.,Interferon-γ (IFN-γ) up-regulates PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumor growth.,In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and changes during the course of anti-PD-1 therapy.,The magnitudes of the early on-treatment increase in circulating exosomal PD-L1, as an indicator of the adaptive response of the tumor cells to T cell re-invigoration, stratifies clinical responders from non-responders.,Our study unveils a mechanism by which tumor cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy.