Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by the release of pro-inflammatory cytokines. Our knowledge of pyroptosis has expanded beyond the cellular level and now includes extracellular responses. In recent years, pyroptosis has attracted considerable attention due to its potential to induce host immunity. For instance, at the 2022 International Medicinal Chemistry of Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled pyroptosis activation (PhotoPyro), an emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share in this Perspective our views on this emerging area and expound on how and why PhotoPyro could trigger antitumor immunity (i.e., turning so-called cold tumors hot). In doing so, we have tried to highlight cutting-edge breakthroughs in PhotoPyro while suggesting areas for future contributions. By providing insights into the current state of the art and serving as a resource for individuals interested in working in this area, it is hoped that this Perspective will set the stage for PhotoPyro to evolve into a broadly applicable cancer treatment strategy.

Automated summary

Pyroptosis is a programmed cell death process characterized by the release of pro-inflammatory cytokines. The recent focus on pyroptosis stems from its potential to induce host immunity, with interest in photon-controlled pyroptosis activation (PhotoPyro) emerging as a strategy for systemic immunity via photoirradiation. In this Perspective, we discuss the current state of PhotoPyro and its potential to trigger antitumor immunity, providing insights and highlighting cutting-edge breakthroughs for future contributions in this area.