NK-92

Immunotherapy

Cancer immunotherapy

Biology

Cancer

Interleukin 21

Interleukin 12

Innate immune system

Natural killer T cell

Cytotoxic T cell

MHC class I

Major histocompatibility complex

Janus kinase 3

In vitro

Immunology

T cell

Innate lymphoid cell

Lymphokine-activated killer cell

Genetics

Biochemistry

Immune system

Cancer cell

Nature reviews. Immunology

Great strides have been made in recent years towards understanding the roles of natural killer (NK) cells in immunity to tumours and viruses. NK cells are cytotoxic innate lymphoid cells that produce inflammatory cytokines and chemokines. By lysing transformed or infected cells, they limit tumour growth and viral infections. Whereas T cells recognize peptides presented by MHC molecules, NK cells display receptors that recognize stress-induced autologous proteins on cancer cells. At the same time, their functional activity is inhibited by MHC molecules displayed on such cells. The enormous potential of NK cells for immunotherapy for cancer is illustrated by their broad recognition of stressed cells regardless of neoantigen presentation, and enhanced activity against tumours that have lost expression of MHC class I owing to acquired resistance mechanisms. As a result, many efforts are under way to mobilize endogenous NK cells with therapeutics, or to provide populations of ex vivo-expanded NK cells as a cellular therapy, in some cases by equipping the NK cells with chimeric antigen receptors. Here we consider the key features that underlie why NK cells are emerging as important new additions to the cancer therapeutic arsenal. This Review explains how natural killer (NK) cells promote immunity to tumours. The authors cover the therapeutic approaches that are being developed to mobilize NK cells in patients with cancer, including NK cell activators, checkpoint blockade, cellular therapies, and bispecific and trispecific NK cell activating antibodies.

Roles of natural killer cells in immunity to cancer, and applications to immunotherapy