Immunoregulatory Mechanisms and Novel Therapeutic Perspectives of the Key Regulator NEK2 in Multiple Myeloma

NIMA associated kinase 2 (NEK2) is a serine/threonine kinase that is associated with inducing chromosomal instability and promoting tumor cell proliferation. It is overexpressed in multiple myeloma (MM) and is associated with bone destruction and poor prognosis. In terms of immune regulation, NEK2 not only promotes MM immune escape by regulating the immune checkpoint PD-L1, but also enhances the immunosuppressive function of tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs) by promoting their differentiation. Meanwhile, NEK2 also affects the T cell immunity of myeloma cells, thereby promoting the occurrence, development, and drug resistance of multiple myeloma. On the contrary, the absence of NEK2 in the microenvironment is associated with B cell immune activation. Given the crucial role of NEK2 in immune evasion and drug resistance formation in multiple myeloma, it has become a strong predictor of drug resistance and poor prognosis, and is expected to become a new target for MM treatment. This article reviews the relevant immune mechanisms and therapeutic prospects of NEK2 in MM, aiming to reveal some of the pathogenesis of MM and provide a theoretical basis for the development of new therapeutic agents targeting NEK2 kinase inhibitors.