Optogenetic engineering for precision cancer immunotherapy.

Cancer immunotherapy has revolutionized oncology, but its full potential remains constrained by treatment resistance, limited durability, immune evasion, and systemic toxicity. Overcoming these obstacles requires innovative strategies for remote and targeted immunomodulation. Opsin-free optogenetics has emerged as a powerful tool in cancer immunotherapy because its versatility and photoactivation kinetics align with the timescale of immune cell signaling, and it has given rise to the subfield of optogenetic immunoengineering. This review explores design strategies and key applications of optogenetic immunoengineering, focusing on the opsin-free optogenetic toolkit in immunotherapy and its ability to modulate the cancer-immunity cycle which is required for amplifying and sustaining antitumor responses. By enabling precise regulation of both innate and adaptive immunity, as demonstrated in recent preclinical studies, optogenetic immunoengineering holds great promise for advancing next-generation precision medicine.