The tumor microenvironment drives NK cell metabolic dysfunction leading to impaired antitumor activity

Article Allergy

Glucocorticoids and the cytokines IL-12, IL-15, and IL-18 present in the tumor microenvironment induce PD-1 expression on human natural killer cells

Linda Quatrini et al.

Summary: The induction of PD-1 expression on human NK cells in the tumor setting is dependent on the cooperative action of glucocorticoids and cytokines, leading to enhanced mRNA translation and increased PD-1 levels.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2021)

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Review Biochemistry & Molecular Biology

NK cells and ILCs in tumor immunotherapy

Simona Sivori et al.

Summary: Innate immune cells, especially NK cells, play an important role in tumor immunotherapy by controlling tumor growth and metastasis. Various approaches have been developed, such as using IL-15 to improve NK cell function and utilizing NK cell engagers to activate NK cells. Additionally, NK cells may express inhibitory checkpoints like PD-1, which can be targeted for therapeutic use against certain tumors.

MOLECULAR ASPECTS OF MEDICINE (2021)

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Article Oncology

Expanded human NK cells from lung cancer patients sensitize patients' PDL1-negative tumors to PD1-blockade therapy

Sophie M. Poznanski et al.

Summary: Expanded natural killer (NK) cells from patients with lung cancer can sensitize non-responding tumors to PD1-blockade therapy by maintaining strong antitumor activity against both PDL1+ and PDL1- patient tumors and overcoming tumor-induced immunosuppression, resulting in synergistic tumor destruction when combined with PD1-blockade.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Cell Biology

Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment

Sophie M. Poznanski et al.

Summary: NK cells play a central role in anti-tumor immunity, but their dysfunction in the tumor microenvironment is a major barrier for cancer immunotherapies. Research showed that human NK cell dysfunction in the tumor microenvironment is caused by suppression of glucose metabolism, and activating the antioxidant pathway can restore NK cell function and enhance anti-tumor activity. Additionally, expanded NK cells with metabolic flexibility not only sustained metabolic fitness but also improved tumor killing in response to nutrient deprivation, showing the potential for exploiting metabolic flexibility in cancer immunotherapy.

CELL METABOLISM (2021)

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Review Biology