Behavioral factors to modulate immunotherapy efficacy in cancer

Immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 therapies, are used to (re)activate the immune system to treat cancer. Despite promising results, a large group of patients does not respond to checkpoint inhibition. In the vulnerability-stress model of behavioral medicine, behavioral factors, such as stress, exercise and classical pharmacological conditioning, predict cancer incidence, recurrence and the efficacy of conventional cancer treatments. Given the important role of the immune system in these processes, certain behavior may be promising to complement immune checkpoint inhibition therapy. Here, we discuss the preliminary evidence and suitability of three behavioral mechanisms, i.e. stress modulation, exercise and classical pharmacological conditioning for the benefit of immunotherapy. It is crucial to study the potential beneficial effects of behavioral strategies that support immunotherapeutic anti-tumor effects with rigorous experimental evidence, to exploit behavioral mechanisms in improving checkpoint inhibition efficacy.