Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade

Area of Science:

• Immunology
• Cancer Biology
• Immunotherapy

Background:

• Checkpoint blockade immunotherapy, particularly targeting the PD-1/PD-L1 axis, has shown significant success in cancer treatment.
• While T cells are recognized for their role, the involvement of other immune cells, like NK cells, is suggested by responses in cancers with low MHC expression.

Purpose of the Study:

• To investigate the impact of PD-1/PD-L1 blockade on natural killer (NK) cells in various mouse cancer models.
• To determine if NK cells contribute to the therapeutic efficacy of PD-1/PD-L1 blockade immunotherapy.

Main Methods:

• Utilized multiple mouse models of cancer, including transplantable, spontaneous, and genetically induced tumors.
• Analyzed PD-1 expression on NK cells and PD-L1 expression on cancer cells.
• Assessed NK cell responses and tumor progression in vivo following PD-1/PD-L1 blockade.

Main Results:

• PD-1/PD-L1 blockade induced a significant NK cell response, which was essential for optimal immunotherapy outcomes.
• PD-1 was found on NK cells across different tumor models; PD-L1 on cancer cells correlated with reduced NK cell activity and more aggressive tumors.
• PD-1 expression was higher on activated NK cells, not exhausted ones, indicating its role in regulating functional responses.

Conclusions:

• The PD-1/PD-L1 axis plays a critical role in inhibiting NK cell activity in the tumor microenvironment.
• NK cells, alongside T cells, are important mediators of PD-1/PD-L1 blockade immunotherapy, highlighting their therapeutic potential in cancer treatment.