PD-L1 blockade enhances anti-tumor efficacy of NK cells

Area of Science:

• Immunology
• Oncology
• Cancer Therapy

Background:

• Anti-programmed death-1 (PD-1)/anti-PD-L1 therapies are effective in cancer treatment but benefit only a subset of patients, typically those with PD-L1 positive tumors.
• Strategies to increase PD-L1 expression and tumor infiltration are needed to expand patient eligibility for these immunotherapies.
• Interferon-gamma (IFNγ), secreted by natural killer (NK) cells, can induce PD-L1 expression on tumors.

Purpose of the Study:

• To investigate if PM21-particle expanded NK cells (PM21-NK cells) can induce PD-L1 expression on ovarian tumors.
• To determine if combining PM21-NK cell therapy with anti-PD-L1 treatment enhances anti-tumor efficacy in an ovarian cancer model.

Main Methods:

• Adoptive transfer of PM21-NK cells into an ovarian cancer model.
• Assessment of PD-L1 expression on tumor cells in vivo.
• In vitro and in vivo evaluation of NK cell cytotoxicity, cytokine secretion, and anti-tumor efficacy in combination with anti-PD-L1 treatment.

Main Results:

• PM21-NK cells secreted high levels of IFNγ and induced PD-L1 expression on SKOV-3 ovarian cancer cells in vivo.
• Anti-PD-L1 treatment significantly improved NK cell anti-tumor efficacy in vivo, despite having no direct effect on PD-1 negative PM21-NK cells in vitro.
• Combination therapy enhanced NK cell persistence and maintained their cytotoxic phenotype within the tumor microenvironment.

Conclusions:

• Combining NK cell therapy with anti-PD-L1 treatment is beneficial regardless of the initial tumor PD-L1 status.
• NK cell therapy can augment the applicability and effectiveness of anti-PD-L1 blockade treatments.
• This combinatorial approach holds promise for improving outcomes in ovarian cancer patients.