Han Wang

Ultrasound-Triggered Azo Free Radicals for Cervical Cancer Immunotherapy

PD-1 blockade is a first-line treatment for recurrent/metastatic cervical cancer but benefits only a small number of patients due to low preexisting tumor immunogenicity. Using immunogenic cell death (ICD) inducers is a promising strategy for improving immunotherapy, but these compounds are limited by the hypoxic environment of solid tumors. To overcome this issue, the nanosensitizer AIBA@MSNs were designed based on sonodynamic therapy (SDT), which induces tumor cell death under hypoxic conditions through azo free radicals in a method of nonoxygen radicals. Mechanistically, the azo free radicals disrupt both the structure and function of tumor mitochondria by reversing the mitochondrial membrane potential and facilitating the collapse of electron transport chain complexes. More importantly, the AIBA@MSN-based SDT serves as an effective ICD inducer and improves the antitumor immune capacity. The combination of an AIBA@MSN-based SDT with a PD-1 blockade has the potential to improve response rates and provide protection against relapse. This study provides insights into the use of azo free radicals as a promising SDT strategy for cancer treatment and establishes a basic foundation for nonoxygen-dependent SDT-triggered immunotherapy in cervical cancer treatment.

Regulatory T Cells in Ovarian Cancer: Insights into Cancer Immunotherapy.

Ovarian cancer (OC) is a formidable malignancy characterized by a notably diminished five-year survival rate. Current evidence demonstrates that OC orchestrates the establishment of an immunosuppressive tumor microenvironment (TME), thereby affording tumor cells a favorable milieu to evade immune surveillance and resist therapeutic interventions. Central to this immunosuppressive landscape are regulatory T cells (Tregs), which infiltrate both tumor sites and circulation. Within the TME, OC cells interact with these Tregs and other immunosuppressive networks to promote tumorigenesis, progression, and metastasis. Recent investigations have predominantly concentrated on elucidating the activation mechanisms and diverse functional states of Tregs across distinct human pathologies. Nevertheless, further study is needed to revolve around the substantial contributions of tumor-infiltrating Tregs in the context of OC. In this review, we provide an overview of present advances in Tregs' heterogeneity and their multifaceted functions within the TME, encompassing immunologic tolerance, immune evasion, metabolic reprogramming, and microenvironmental remodeling. By integrating TME and therapy perspectives on Tregs in OC, this review bridges existing gaps in the literature and aims to offer emerging insights for precise immunotherapeutic strategies specifically for OC.