Although immunotherapy, including immune checkpoint inhibitors, has revolutionized cancer treatment, only a small percentage of patients show sustained response. Recently, we have shown that photobiomodulation (PBM) with near-infrared (NIR) light in the NIR-II window reduces oxidative stress and supports CD8+ T cell proliferation, suggesting that PBM with NIR-II light may enhance anticancer immunity. In this study, we report a novel approach to support tumor-infiltrating CD8+ T cells by PBM using NIR-II laser with high tissue penetration depth. Lasers are a safe and low-cost therapy that can be used in combination with a broad range of other therapies without modification.
Since biological chromophores typically show several absorption peaks, the specific effects of photobiomodulation would be induced with a combination of two wavelengths, rather than a single wavelength of near-infrared (NIR) light.
Single cell live imaging of T cells treated with a combination of 1064 and 1270 nm NIR lasers revealed that the treatment modulated intracellular calcium and reactive oxygen species (ROS) in T cells, which are known to be critical regulators of their function.
The treatment with a specific combination of NIR wavelengths of low power laser could be further explored for therapeutic purposes including immunotherapy for cancer and allergy.
There remains a paucity of methodological tools to determine the biodistribution of vaccine antigens. In response to this, we established a near-infrared (NIR) imaging method using a NIR fluorophore, ZW800-1C, conjugated with different sizes of vaccine antigens that allows for real-time monitoring of the fate of delivered vaccines in vivo. The fluorescent signal observed using the system after a model vaccine injection in mice recapitulated the size-dependent transport of the vaccine into the secondary lymphoid tissue. This methodology can be broadly applied for optimization of formulations and safety evaluation of clinical vaccines.
Significance: Photobiomodulation is a well-established therapeutic modality. However, the mechanism of action is poorly understood, due to lack of research in the causal relationship between the near-infrared (NIR) light irradiation and its specific biological effects, hindering broader applications of this technology.
Aim: Since biological chromophores typically show several absorption peaks, we determined whether specific effects of photobiomodulation are induced with a combination of two wavelengths at a certain range of irradiance only, rather than a single wavelength of NIR light.
Approach: In order to analyze a wide array of combinations of multispectral NIR light at various irradiances efficiently, we developed a new optical platform equipped with two distinct wavelengths of NIR lasers by high-throughput multiple dosing for single-cell live imaging. Two wavelengths of 1064 and 1270 nm were selected based on their photobiomodulatory effects reported in the literature.
Results: A specific combination of wavelengths at low irradiances (250 to 400 mW / cm2 for 1064 nm and 55 to 65 mW / cm2 for 1270 nm) modulates mitochondrial retrograde signaling, including intracellular calcium and reactive oxygen species in T cells. The time-dependent density functional theory computation of binding of nitric oxide (NO) to cytochrome c oxidase indicates that the illumination with NIR light could result in the NO release, which might be involved in these changes.
Conclusions: This optical platform is a powerful tool to study causal relationship between a specific parameter of NIR light and its biological effects. Such a platform is useful for a further mechanistic study on not only photobiomodulation but also other modalities in photomedicine.
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