Reviving Dormant Immunity: Millimeter Waves Reprogram the Immunosuppressive Microenvironment to Potentiate Immunotherapy without Obvious Side Effects

Addressing the variability in cancer immunotherapeutic outcomes among patients and the challenge of devising safe strategies to overcome immune evasion in solid tumors are crucial in advancing cancer therapy. This study investigated the anti-tumor effect of millimeter waves (MMWs) alone and in combination with the anti-programmed cell death-ligand 1 (α-PD-L1) antibody in a 4T1 “cold tumor” model. The results show that MMWs not only inhibit tumor growth but also improve tumor metabolism and the immune microenvironment and enhance anti-tumor immune responses by inducing conformational changes of key immune proteins. Further experiments conducted on cellular and animal models demonstrated that the anti-tumor efficacy of MMWs, which plays a pivotal role, was substantially enhanced with the aid of α-PD-L1. This collaboration resulted in a synergistic effect that not only inhibited tumor progression but also promoted a sustained immune response and prevented recurrence. The additional CT26 “cold tumor” model validates the applicability of this strategy across other “cold tumor” types, particularly in reprogramming the immunosuppressed state of “cold tumor”. These findings underscore the unique potential of MMWs as a nonionizing, nonthermal therapeutic tool that complements cancer immunotherapy, offering a novel approach for the precision treatment of solid tumors.