Optogenetic Immunomodulation: Shedding Light on Antitumor Immunity

Abstract

Microbial opsin-based optogenetic tools have been transformative for neuroscience. To extend optogenetic approaches to the immune system to remotely control immune responses with superior spatiotemporal precision, pioneering tools have recently been crafted to modulate lymphocyte trafficking, inflammasome activation, dendritic cell maturation, and antitumor immunity through the photoactivation of engineered chemokine receptors and calcium release-activated calcium channels. We highlight herein some conceptual design strategies for installing light sensitivities into the immune signaling network, and in parallel, we propose potential solutions for in vivo optogenetic applications in living organisms with near-infrared light-responsive upconversion nanomaterials. Moreover, to move beyond proof-of-concept into translational applications, we discuss future prospects for integrating personalized immunoengineering with optogenetics to overcome critical hurdles in cancer immunotherapy.

Optogenetic toolkit for precise control of calcium signaling

“…However, the spatial resolution might be compromised owing to the rapid diffusion of caged compounds in the cytoplasm. Hurdles hampering the application of caged compounds in vivo include irreversibility, low delivery efficiency, limited depth of tissue penetration and strong phototoxicity associated with UV irradiation [24–26, 36]. …”

Remote Control of Mammalian Cells with Heat-Triggered Gene Switches and Photothermal Pulse Trains

“…46 Looking forward, this framework of activating gene expression by heat provides an orthogonal mechanism to control cellular activity in addition to small-molecule 47 or light-based methods. 13 Such platforms may be integrated across different immune cell types for remote control of synthetic immunological systems.…”

Therapeutic Potential of Optogenetic Treatment for Individuals with Multiple Sclerosis

“…However, while optogenetics may treat these symptoms, this review does not intend to demonstrate the effect of photostimulation on the autoimmune function of the disorder. To our knowledge, literature documenting immunomodulation using optogenetics is lacking, and what has been published only discusses proof-of-concept and designs for future development (Tan, He, Han, & Zhou, 2017). The approaches involve optogenetic control of immune responses with novel tools that modulate lymphocyte trafficking, inflammasome activation, dendritic cell (DC) maturation, and antitumor immunity (Tan et al, 2017).…”

“…To our knowledge, literature documenting immunomodulation using optogenetics is lacking, and what has been published only discusses proof-of-concept and designs for future development (Tan, He, Han, & Zhou, 2017). The approaches involve optogenetic control of immune responses with novel tools that modulate lymphocyte trafficking, inflammasome activation, dendritic cell (DC) maturation, and antitumor immunity (Tan et al, 2017). Further information on the theoretical methods involving the combination of optogenetics and immunoengineering, termed optoimmunoengineering, can be found in the review conducted by Tan et al (2017) The most common cognitive impairment seen in MS is visual learning and memory (Chiaravalloti & Deluca, 2008).…”

“…The approaches involve optogenetic control of immune responses with novel tools that modulate lymphocyte trafficking, inflammasome activation, dendritic cell (DC) maturation, and antitumor immunity (Tan et al, 2017). Further information on the theoretical methods involving the combination of optogenetics and immunoengineering, termed optoimmunoengineering, can be found in the review conducted by Tan et al (2017) The most common cognitive impairment seen in MS is visual learning and memory (Chiaravalloti & Deluca, 2008). Evidence has shown the problem lies in the initial learning of the memories as memory recall in MS patients is equal to healthy individuals, indicating that long-term memory systems are relatively intact (Chiaravalloti & Deluca, 2008).…”