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Current progress in NK cell biology and NK cell-based cancer immunotherapy

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

A better understanding of the complex interactions between the immune system and tumour cells from different origins has opened the possibility to design novel procedures of antitumoral immunotherapy. One of these novel approaches is based on the use of autologous or allogeneic natural killer (NK) cells to treat cancer. In the last decade, different strategies to activate NK cells and their use in adoptive NK cell-based therapy have been established. Although NK cells are often considered as a uniform cell population, several phenotypic and functionally distinct NK cells subsets exist in healthy individuals, that are differentially affected by ageing or by apparently innocuous viruses such as cytomegalovirus (CMV). In addition, further alterations in the expression of activating and inhibitory receptors are found in NK cells from cancer patients, likely because of their interaction with tumour cells. Thus, NK cells represent a promising strategy for adoptive immunotherapy of cancer already tested in phase 1/2 clinical trials. However, the existence of NK cell subpopulations expressing different patterns of activating and inhibitory receptors and different functional capacities, that can be found to be altered not only in cancer patients but also in healthy individuals stratified by age or CMV infection, makes necessary a personalized definition of the procedures used in the selection, expansion, and activation of the relevant NK cell subsets to be successfully used in NK cell-based immunotherapy.

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Abbreviations

AML:

Acute myeloid leukaemia

ADCC:

Antibody-dependent cell cytotoxicity

Anti-TAA:

Anti-tumour-associated antigens

APCs:

Antigen-presenting cells

CAR:

Chimeric antigen receptor

CMV:

Cytomegalovirus

EGFR:

Epidermal growth factor receptor

GMP:

Good manufacturing practice

GvHD:

Graft-versus-host disease

HCMV:

Human cytomegalovirus

HLA:

Human leukocyte antigen

HSCT:

Hematopoietic stem cell transplantation

KIR:

Killer cell immunoglobulin-like receptors

LAG-3:

Lymphocyte-activating gene 3

MHC:

Major histocompatibility complex

MCMV:

Murine cytomegalovirus

MM:

Multiple myeloma

NCRs:

Natural cytotoxicity receptors

NHL:

Non-Hodgkin lymphoma

NK:

Natural killer

PD-1:

Programmed death-1

TAA:

Tumour-associated antigen

TIGIT:

T cell immunoreceptor with Ig and ITIM domains

TIM-3:

T cell immunoglobulin and mucin domain 3

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Funding

This work was supported by: Instituto de Salud Carlos III, Spain (PI13/02691 to Rafael Solana and PI16/01615 to Rafael Solana and Corona Alonso). Agencia Estatal de Investigación, Ministry of Economy and Competitiveness of Spain (SAF2013-46161-R and SAF2017-87538-R to Raquel Tarazona). Consejería de Economía e Infraestructuras, Junta de Extremadura (IB16164 and grants to INPATT (CTS040) research group GR18085 to Raquel Tarazona). Grants were cofinanced by European Regional Development Funds (FEDER) “Una manera de hacer Europa”. Grant TE-0039-18 (to Beatriz Guerrero) from Consejería de Educación y Empleo cofinanced by European Social Fund, Youth Employment Initiative, “El FSE invierte en tu futuro”. Plan Propio Universidad de Córdoba (to Alejandra Pera).

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RT, CA and RS designed the first draft of the manuscript. NL, BG, FH and IV contributed to the writing of different sections, figures and tables. AP, BS, NP and ED discussed the manuscript sections and contributed with updated references. All authors revised and agreed to the final version of the paper.

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Correspondence to Raquel Tarazona, Corona Alonso or Rafael Solana.

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Tarazona, R., Lopez-Sejas, N., Guerrero, B. et al. Current progress in NK cell biology and NK cell-based cancer immunotherapy. Cancer Immunol Immunother 69, 879–899 (2020). https://doi.org/10.1007/s00262-020-02532-9

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