BCG immunotherapy promotes tumor-derived T-cell activation through the FLT3/FLT3LG pathway in bladder cancer

Abstract

Bladder instillation therapy is a common treatment for superficial or nonmuscle invasive bladder cancer. After surgery or reresection, chemotherapy drugs (epirubicin) or medications such as Bacillus Calmette-Guérin (BCG) are used for bladder instillation therapy, which can reduce the risk of bladder cancer recurrence and progression. However, the specific mechanism by which BCG stimulates the antitumor response has not been thoroughly elucidated. Additionally, although BCG immunotherapy is effective, it is difficult to predict which patients will have a positive response. In this study, we explored the BCG-induced immune response and found that high levels of Fms-related receptor tyrosine kinase 3 ligand (FLT3LG) were expressed after BCG treatment. This FLT3LG can directly act on CD8 + T cells and promote their proliferation and activation. The use of FLT3 inhibitors can neutralize the antitumor effects of BCG. In vitro experiments showed that FLT3LG can synergize with T-cell receptor activators to promote the activation of tumor-derived T cells. This study partially elucidates the mechanism of CD8 + T-cell activation in BCG immunotherapy and provides a theoretical basis for optimizing BCG instillation therapy in bladder cancer

The causal relationship between immune cells mediating FIT3L, CCL4, OSM, and skin‐derived deteriorated tumors

“… 39 Notably, Zhang et al. 40 discovered in a BCG immunotherapy study for bladder cancer that FLT3LG enhances the ex vivo activation of CD8 T cells, providing a novel candidate target for future optimization of cancer treatments. This research delves into the critical role of Flt3L in regulating CD4+ CD8dim T cell percentage in leukocytes, unveiling the genetic mechanisms by which it inhibits the progression of BCC.…”