NK Cell-Targeted Immunotherapies in Bladder Cancer: Beyond Checkpoint Inhibitors.

Area of Science:

• Oncology
• Immunology
• Cancer Therapy

Background:

• Immunotherapies, including immune checkpoint inhibitors (ICIs), are crucial for bladder cancer treatment.
• Existing T cell-targeted ICIs show limited response rates, necessitating complementary strategies.
• Natural killer (NK) cells present a promising approach due to their rapid, receptor-mediated antitumor activity.

Purpose of the Study:

• To review current NK cell-targeted immunotherapies for bladder cancer.
• To explore strategies like engineered viral vectors, small molecules, NK agonist antibodies, interleukins, and CAR-NK cells.
• To assess their potential to enhance immunotherapy efficacy in bladder cancer.

Main Methods:

• Literature review of NK cell roles in solid tumors and hematologic malignancies.
• Summarized knowledge on NK cell-based immunotherapies for bladder cancer.
• Identified novel therapeutic strategies leveraging NK cell functions.

Main Results:

• NK cells significantly influence the tumor microenvironment (TME).
• Exploiting NK cell functions can augment T cell-targeted immunotherapies.
• NK cell activity is regulated by HLA class I, KIR, and NKG2A receptors.

Conclusions:

• NK cells are a key target for improving bladder cancer immunotherapy.
• Further research on NK cell profiling can identify optimal patient candidates for NK-targeted therapies.
• Exploiting NK cell antitumor properties holds significant therapeutic potential.