Cancer Immunology, Immunotherapy

, Volume 68, Issue 5, pp 861–870 | Cite as

Modulation of NK cells with checkpoint inhibitors in the context of cancer immunotherapy

  • Beatriz Sanchez-Correa
  • Nelson Lopez-Sejas
  • Esther Duran
  • Fernando Labella
  • Corona Alonso
  • Rafael SolanaEmail author
  • Raquel Tarazona
Focussed Research Review


The incidence of some types of tumours has increased progressively in recent years and is expected to continue growing in the coming years due in part to the aging of the population. The design of new therapies based on natural killer (NK) cells opens new possibilities especially for the treatment of elderly patients who are particularly susceptible to the toxicity of conventional chemotherapy treatments. In recent years, the potential use of NK cells in cancer immunotherapy has been of great interest thanks to advances in the study of NK cell biology. The identification of key points (checkpoints) in the activation of NK cells that can be regulated by monoclonal antibodies has allowed the design of new therapeutic strategies based on NK cells. However, there are still limitations for its use and the first clinical trials blocking KIR inhibitory receptors have shown little efficacy by inhibiting the maturation of NK cells. Blockade of other inhibitory receptors such as TIGIT, TIM3, LAG3 and PD1 may represent novel strategies to increase NK function in cancer patients. Altogether, the identification of NK cell and tumour cell markers of resistance or susceptibility to the action of NK cells will contribute to identifying those patients that will most likely benefit from NK cell-based immunotherapy.


NK cells miRNA Immunotherapy Checkpoint blockade PIVAC 17 



Acute myeloid leukaemia


Chimeric antigen receptor


Cytotoxic T lymphocytes


Human leukocyte antigen






Killer cell immunoglobulin-like receptors


Lymphocyte activating gene 3


Major histocompatibility complex




Monoclonal antibody


Natural cytotoxicity receptors


Natural killer


Non-small cell lung cancer


Programmed death-1


T cell immunoglobulin and mucin domain 3


T cell immunoreceptor with Ig and ITIM domains


Author contributions

BS-C, RS and RT designed and wrote the first draft of the manuscript. NL-S, ED, FL and CA discussed the manuscript sections and contributed with updated references. All authors revised and agreed the final version of the paper.


This work was supported by Grants PI13/02691 (to Rafael Solana), PI16/01615 (to Rafael Solana and Corona Alonso) by Instituto de Salud Carlos III, SAF2013-46161-R and SAF2017-87538-R (to Raquel Tarazona) from the Agencia Estatal de Investigacion (Ministry of Economy and Competitiveness of Spain), IB16164 and Grants to INPATT (CTS040) research group (GR18085) from Consejeria de Economia e Infraestructura (Junta de Extremadura) (to Raquel Tarazona), cofinanced by European Regional Development Funds (FEDER) “Una manera de hacer Europa”.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Immunology UnitUniversity of ExtremaduraCaceresSpain
  2. 2.Histology and Pathology Unit, Faculty of VeterinaryUniversity of ExtremaduraCaceresSpain
  3. 3.Immunology UnitUniversidad de CordobaCordobaSpain
  4. 4.Instituto Maimónides de Investigación Biomédica (IMIBIC)CórdobaSpain
  5. 5.Reina Sofia University HospitalCórdobaSpain

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