Iron tribe.

Virtually all the data we currently have, be what it may, on the subject suggests a powerful synergy with the combination of immune checkpoint inhibition (ICI) and radiation therapy. The most popular theories behind this synergism have focused on how radiation helps the systemic efficacy of ICI by kickstarting a host-tumor immune response through amplification of tumor antigen presentation. Here’s a neat study demonstrating the reverse: how ICI helps radiation do its job locally. It all centers on ferroptosis. Say wha? It’s a little known but still fatal pathway of cell death resulting from an iron-dependent (thus the name) accumulation of lipid peroxide. This potential component of the interrelationship between ICI and radiation clicked in these authors’ minds when they noted CD8+ T cells modulate tumoral ferroptosis, which also happens to be a mechanism of cell death following radiation. Here they actually show that ICI enhances tumor death via increased ferroptosis following local radiation. More specifically, (1) ICI ramped up interferon-Ɣ release from C8+ T-cell while (2) radiation ramped up ATM, and together these pathways synergistically reduced cystine uptake → enhancing tumor lipid oxidation → increasing ferroptosis → improving tumor control. In case you want more, here’s a ferroptosis video to watch during your next scalp massage. TBL: Ferroptosis is a slick pathway of radiation-induced cell death that looks to be enhanced by ICI. | Lang, Cancer Discov 2019