Strategies to Augment Natural Killer (NK) Cell Activity against Solid Tumors

The immune system plays a crucial role to prevent local growth and dissemination of cancer. Therapies based on activating the immune system can result in beneficial responses in patients with metastatic disease. Treatment with antibodies targeting the immunological checkpoint axis PD-1 / PD-L1 can r...

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Bibliographic Details
Published in:Cancers 2019-07, Vol.11 (7), p.1040
Main Authors: Chen, Ziqing, Yang, Ying, Liu, Lisa L, Lundqvist, Andreas
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Antigen presentation
Antigen processing
Apoptosis
Cancer
Cell activation
Clinical trials
Cytokines
Cytotoxicity
Gene expression
Hematology
Immune checkpoint
Immune system
Immunotherapy
Interferon
Ligands
Lymphocytes
Lymphocytes T
Medicin och hälsovetenskap
Metastases
Myeloid leukemia
Natural killer cells
Patients
PD-1 protein
PD-L1 protein
Polyethylene glycol
Review
Solid tumors
Tumor cells
Tumor necrosis factor-TNF
Tumors
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Summary:The immune system plays a crucial role to prevent local growth and dissemination of cancer. Therapies based on activating the immune system can result in beneficial responses in patients with metastatic disease. Treatment with antibodies targeting the immunological checkpoint axis PD-1 / PD-L1 can result in the induction of anti-tumor T cell activation leading to meaningful long-lasting clinical responses. Still, many patients acquire resistance or develop dose-limiting toxicities to these therapies. Analysis of tumors from patients who progress on anti-PD-1 treatment reveal defective interferon-signaling and antigen presentation, resulting in immune escape from T cell-mediated attack. Natural killer (NK) cells are innate lymphocytes that can kill tumor cells without prior sensitization to antigens and can be activated to kill tumor cells that have an impaired antigen processing and presentation machinery. Thus, NK cells may serve as useful effectors against tumor cells that have become resistant to classical immune checkpoint therapy. Various approaches to activate NK cells are being increasingly explored in clinical trials against cancer. While clinical benefit has been demonstrated in patients with acute myeloid leukemia receiving haploidentical NK cells, responses in patients with solid tumors are so far less encouraging. Several hurdles need to be overcome to provide meaningful clinical responses in patients with solid tumors. Here we review the recent developments to augment NK cell responses against solid tumors with regards to cytokine therapy, adoptive infusion of NK cells, NK cell engagers, and NK cell immune checkpoints.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11071040