Alleviating Tumor Hypoxia and Immunosuppression via Sononeoperfusion: A New Ally for potentiating anti-PD-L1 blockade of solid Tumor

作者：Guoliang Yang, Hui Li, Jiabei Yin, Yao Lei, Jun Yang, Jiawei Tang, You Wu, Meng Zhou, Tingting Luo, Yi Zhang, Jing Zhang, Xuezhi Yang, Xiaoxiao Dong, Zheng Liu, Ningshan Li · 发表于：Ultrasonics Sonochemistry · 年份：2024 · DOI：10.1016/j.ultsonch.2024.107115 · 被引用次数：14 · 研究领域：Nanoplatforms for cancer theranostics、Cancer, Hypoxia, and Metabolism、Ultrasound and Hyperthermia Applications

• Sononeoperfusion refers to tumor perfusion enhancement by ultrasound stimulated microbubble cavitation. • Sononeoperfusion is a promising method to alleviate tumor hypoxia and immunosuppression. • The mechanism by which sononeoperfusion modulates the tumor immune microenvironment may be associated with the induction of tumor vascular normalization. • Sononeoperfusion way can be easily translated to clinic for facilitating immunotherapy. The hypoxic and immunosuppressive tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we found that sononeoperfusion—a new effect of tumor perfusion enhancement induced by low mechanical index ultrasound stimulated microbubble cavitation (USMC)—ameliorated tumor tissue oxygenation and induced tumor vascular normalization (TVN). This TVN might be associated with the down-regulation of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) within tumors. Moreover, the sononeoperfusion effect reduced the accumulation of immunosuppressive cells, such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (M2-TAMs), and decreased the production of immune inhibitory factors like transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10), chemoattractant chemokines CC-chemokine ligand 22 (CCL22), CCL28, adenosine and lactate within tumors. Notably, flow cytometry analysis revealed that sononeoperfusion not only incr...