NK cells and ILCs in tumor immunotherapy

Area of Science:

• Immunology
• Oncology
• Cancer Immunotherapy

Background:

• Innate immunity cells, especially Natural Killer (NK) cells, are vital in tumor immunotherapy.
• NK cells possess potent cytolytic activity against tumors, leading to various therapeutic strategies.
• Previous approaches using adoptive NK cell transfer with IL-2 showed limited success due to toxicity and regulatory T cell expansion.

Purpose of the Study:

• To explore novel strategies for harnessing NK cell functions in cancer immunotherapy.
• To overcome limitations of existing NK cell-based therapies.
• To evaluate the role of innate immunity, including NK cells and innate lymphoid cells (ILCs), in cancer treatment.

Main Methods:

• Review of various approaches to enhance NK cell activity, including IL-15-based therapies, TLR stimulation, and bispecific/trispecific NK cell engagers (BiKEs/TriKEs).
• Investigation of therapeutic use of checkpoint inhibitors (e.g., anti-PD-1) to activate NK cells against tumors.
• Exploration of 'adaptive' NK cells and chimeric antigen receptor (CAR)-engineered NK cells (CAR-NK) for cancer therapy.

Main Results:

• IL-15 and modified IL-15 molecules offer potential to overcome IL-2 limitations.
• BiKEs/TriKEs and checkpoint inhibitors (targeting PD-1/PD-L1) show promise in activating NK cells against tumors, especially those lacking HLA class I expression.
• Adaptive NK cells and CAR-NK cells (allogeneic, non-GvHD inducing) present significant advancements for off-the-shelf cancer treatments.
• Certain innate lymphoid cells (ILCs), particularly ILC3 subsets, may correlate with better prognosis in non-small cell lung cancer (NSCLC).

Conclusions:

• NK cells represent a versatile and powerful tool in modern cancer immunotherapy.
• Emerging strategies like CAR-NK and checkpoint inhibition are expanding the therapeutic potential of innate immunity against various cancers.
• Innate immunity, through NK cells and potentially ILCs, is poised to significantly contribute to future cancer cure advancements.