NK Cells in Myeloproliferative Neoplasms (MPN)

Naismith, Erin; Steichen, Janine; Sopper, Sieghart; Wolf, Dominik

SIMPLE SUMMARY: NK cells are important innate immune effectors that contribute substantially to tumor control, however the role of NK cells in haematological cancers is not as well understood. The aim of this review is to highlight the importance of the role of NK cells in the management of Ph+ Myeloproliferative Neoplasms, and emphasize the need and possible benefits of a more in-depth investigation into their role in classical MPNs and show potential strategies to harness the anti-tumoral capacities of NK cells. 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.