NK Cells in Myeloproliferative Neoplasms (MPN)

Abstract

Myeloproliferative neoplasms (MPNs) comprise a heterogenous group of hematologic neoplasms which are divided into Philadelphia positive (Ph+), and Philadelphia negative (Ph-) or classical MPNs. A variety of immunological factors including inflammatory, as well as immunomodulatory processes, closely interact with the disease phenotypes in MPNs. NK cells are important innate immune effectors and substantially contribute to tumor control. Changes to the absolute and proportionate numbers of NK cell, as well as phenotypical and functional alterations are seen in MPNs. In addition to the disease itself, a variety of therapeutic options in MPNs may modify NK cell characteristics. Reports of suppressive effects of MPN treatment strategies on NK cell activity have led to intensive investigations into the respective compounds, to elucidate the possible negative effects of MPN therapy on control of the leukemic clones. We hereby review the available literature on NK cells in Ph+ and Ph- MPNs and summarize today's knowledge on disease-related alterations in this cell compartment with particular focus on known therapy-associated changes. Furthermore, we critically evaluate conflicting data with possible implications for future projects. We also aim to highlight the relevance of full NK cell functionality for disease control in MPNs and the importance of considering specific changes related to therapy in order to avoid suppressive effects on immune surveillance.

Keywords: CML; Innate immunity; essential thrombocythemia; polycythemia vera; primary myelofibrosis.

Figure 1

Phenotypic and functional alterations in the NK cell compartment of CML patients before therapy initiation, as well as TKI-specific changes. An in vivo increase or decrease is displayed with green or red arrows respectively, while blue and purple arrows indicate an observed increase or decrease in vitro or using a mouse model. References are given in brackets. Created with BioRender.com (accessed on 15 June 2021).

Figure 2

NK-cell associated changes serving as prognostic factors for molecular response or treatment free remission in CML. Green arrows indicate a favorable effect of an increase in the respective marker, while red arrows demonstrate that a decrease is beneficial to achieving molecular remission or treatment free remission. A circled green cross or red minus indicate a positive prognostic value of either the expression or absence respectively, of a certain marker. References are shown in brackets. Created with BioRender.com (accessed on 15 June 2021). * refers to the genetic mutation.

Figure 3

In vivo alterations to the NK cell compartment of Ph− MPNs before therapy initiation, as well as with IFNα or ruxolitinib therapy. Green arrows represent an increase in the frequency of specific properties observed, while red indicate a decrease or impairment, and yellow indicates no change. References are displayed in brackets. Created with BioRender.com (accessed on 15 June 2021).