Exploiting temporal aspects of cancer immunotherapy

Abstract

Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. To improve outcomes, a multitude of clinical trials are testing combinations of ICT with various other treatment modalities. Ideally, those combination treatments should take time-dependent immunological events into account. Recent studies have started to map the dynamic cellular and molecular changes that occur during treatment with ICT, in the tumour and systemically. Here, we overlay the dynamic ICT response with the therapeutic response following surgery, radiotherapy, chemotherapy and targeted therapies. We propose that by combining treatments in a time-conscious manner, we may optimally exploit the interactions between the individual therapies. The tumour immune microenvironment greatly affects responses to immune checkpoint therapies. In this Perspective, Zemek et al. explore the dynamic changes in response to both immunotherapy and conventional treatment and advocate for strategic combination therapies over time to enhance antitumour immune responses.