NK cells and solid tumors: therapeutic potential and persisting obstacles

Area of Science:

• Immunology
• Cancer Biology
• Cellular Metabolism

Background:

• Natural killer (NK) cells are innate lymphocytes with cytotoxic potential, emerging as promising anticancer therapeutics.
• While NK cell infusions yield positive results in leukemia patients, their efficacy against solid tumors remains limited.
• Factors within the tumor microenvironment (TME) hinder NK cell infiltration, persistence, and activation.

Purpose of the Study:

• To review the metabolic and cellular barriers inhibiting NK cell activity in solid tumors.
• To discuss strategies for overcoming these obstacles to enhance NK cell-based cancer therapy.

Main Methods:

• Literature review of preclinical and clinical data.
• Analysis of factors affecting NK cell function in the TME.
• Exploration of therapeutic strategies to enhance NK cell efficacy.

Main Results:

• The TME presents metabolic challenges (hypoxia, adenosine, ROS, prostaglandins) that impair NK cell function.
• Cellular components within the TME (fibroblasts, macrophages, MDSCs, Tregs) actively suppress NK cell-mediated immunity.
• Inadequate tumor infiltration and persistence are key limitations for NK cell therapy in solid malignancies.

Conclusions:

• Overcoming metabolic and cellular suppressive mechanisms in the TME is crucial for improving NK cell therapy.
• Developing strategies to enhance NK cell infiltration, activation, and persistence can lead to superior therapeutic outcomes in solid tumors.