The article investigates the combination therapy of zoledronic acid and thymosin α1 in enhancing antitumor immunity against prostate cancer. Results show that the combination treatment reprograms the tumor microenvironment improving therapeutic outcomes in patients with advanced or metastatic prostate cancer.

Prostate cancer (PCa) is one of the most commonly diagnosed malignancies and a major cause of cancer-related death in men in Western countries. It is an incurable malignancy with high lethality and a poor prognosis, particularly in advanced or metastatic stages. Androgen deprivation therapy (ADT) is the primary treatment for advanced or metastatic prostate cancer, but patients often develop resistance to this therapy, leading to a more aggressive state with bone metastases. Patients with prostate cancer typically have immune cold tumors, characterized by scarce T-cell infiltration in the tumor microenvironment, making them less responsive to immunotherapy.

ADT is a primary treatment approach for advanced or metastatic prostate cancer. It involves reducing the levels of male hormones, specifically androgens, in the body to slow down or stop the growth of cancer cells. This therapy is commonly used in patients with prostate cancer as the androgen receptor plays a crucial role in the development and progression of the disease.

The MyD88/NF-κB signaling pathway plays a crucial role in the immunostimulatory functions of Zoledronic acid (ZA) and thymosin α1 (Tα1) therapy in prostate cancer tumors. The study shows that ZA and Tα1 treatment inhibits the activation of the MyD88/NF-κB pathway in PCa cells, thereby decreasing the expression of anti-inflammatory and immunosuppressive cytokines while increasing the levels of pro-inflammatory cytokines and chemokines associated with lymphocyte infiltration. This reprogramming of the tumor microenvironment from immune cold to T-cell-inflamed enhances antitumor immunity.

Furthermore, the combination therapy of ZA and Tα1 promotes the activation of the MyD88/NF-κB pathway in macrophages and T cells, leading to the polarization of macrophages into a pro-inflammatory phenotype and increased cytotoxic function of T cells. These findings suggest that ZA and Tα1 elicit antitumor immune effects by differentially modulating the MyD88/NF-κB signaling pathway in various cells within the tumor microenvironment.

Overall, the MyD88/NF-κB signaling pathway acts as a key mediator in the immunostimulatory functions of ZA and Tα1 therapy in PCa tumors, facilitating the enhancement of antitumor immunity and potentially improving therapeutic outcomes in patients with aggressive PCa.

Full article can be found here: https://doi.org/10.1136/jitc-2022-006381