Reviving dormant immunity: Millimeter waves reprogram the immunosuppressive microenvironment to potentiate immunotherapy without obvious side effects

MMWs, a form of non-ionizing, non-thermal electromagnetic radiation, have emerged as a promising solution. Operating at a frequency of 35 GHz with an energy density of ≤10 mW/cm², MMWs do not raise tissue temperatures or cause cellular damage. Instead, they interact with biological macromolecules (e.g., proteins, DNA) through resonance absorption, inducing conformational changes that modulate their function. In preclinical studies using 4T1 breast cancer and CT26 colorectal cancer models—both classic "cold tumors"—researchers found that MMW irradiation alone inhibited tumor growth in a time-dependent manner. A 30-minute daily irradiation session led to a significant reduction in tumor volume and weight, with no observable systemic toxicity or weight loss in experimental mice.

The study uncovered multiple mechanisms underlying MMWs' anti-tumor effects: (1) Protein Conformational Modulation: MMWs induce structural changes in key immune proteins (CD47, CD38, TGF-β), disrupting their ability to mediate immune escape. For example, CD47—a "don't eat me" signal on tumor cells—loses its binding affinity to the SIRPα receptor on macrophages after MMW exposure, enabling phagocytosis of tumor cells; (2) Metabolic Reprogramming: MMW irradiation reduces levels of choline and carnitine, metabolites essential for tumor cell membrane synthesis and energy metabolism, starving tumors of vital nutrients. (3) Immune Microenvironment Remodeling: MMWs increase infiltration of anti-tumor immune cells (mature dendritic cells, CD8⁺ T cells, NK cells) while reducing immunosuppressive populations (regulatory T cells, M2-type macrophages), converting "cold tumors" into immunologically active "hot tumors."

When combined with the immune checkpoint inhibitor α-PD-L1, MMWs demonstrated a powerful synergistic effect. The combination therapy achieved a tumor suppression rate of up to 90% in 4T1 models, outperforming either treatment alone. Key outcomes included: (1) Inhibition of primary tumor growth and distant metastasis; (2) Induction of long-term anti-tumor immune memory, reducing recurrence risk after tumor resection; (3) Enhanced secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-6) that amplify immune responses. In bilateral tumor models, treating only one tumor with the MMW-α-PD-L1 combination suppressed growth in both the treated and untreated tumors, confirming a systemic immune response.

"The non-invasive and safe nature of MMW therapy, combined with its ability to boost immunotherapy efficacy, makes it a game-changer for cancer treatment," said Zhenqi Jiang, corresponding author of the study and professor at the Beijing Institute of Technology. "Our findings validate its potential across multiple 'cold tumor' types, addressing a critical unmet need in oncology." The therapy’s favorable safety profile—no damage to major organs or liver/kidney function—positions it as a viable option for patients who cannot tolerate traditional chemotherapy or radiation. Future research will focus on optimizing MMW parameters (frequency, duration) and advancing clinical trials to evaluate efficacy in human patients.

Authors of the paper include Zhenqi Jiang, Rui Jing, Ozioma Udochukwu Akakuru, Keyi Li, and Xiaoying Tang.

This work was supported by the National Natural Science Foundation of China (32101153), the Young Elite Scientists Sponsorship Program by BATSA (BYESS2023244), and the Beijing Institute of Technology Research Fund Program for Young Scholars.

The paper, “Reviving Dormant Immunity: Millimeter Waves Reprogram the Immunosuppressive Microenvironment to Potentiate Immunotherapy without Obvious Side Effects” was published in the journal Cyborg and Bionic Systems on Dec 10, 2025, at DOI: 10.34133/cbsystems.0468.

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