Novel immune modulators used in hematology: impact on NK cells

Abstract

There is a wide range of important pharmaceuticals used in treatment of cancer. Besides their known effects on tumor cells, there is growing evidence for modulation of the immune system. Immunomodulatory drugs (IMiDs®) play an important role in the treatment of patients with multiple myeloma or myelodysplastic syndrome and have already demonstrated antitumor, anti-angiogenic, and immunostimulating effects, in particular on natural killer (NK) cells. Tyrosine kinase inhibitors are directly targeting different kinases and are known to regulate effector NK cells and expression of NKG2D ligands (NKG2DLs) on tumor cells. Demethylating agents, histone deacetylases, and proteasome inhibitors interfere with the epigenetic regulation and protein degradation of malignant cells. There are first hints that these drugs also sensitize tumor cells to chemotherapy, radiation, and NK cell-mediated cytotoxicity by enhanced expression of TRAIL and NKG2DLs. However, these pharmaceuticals may also impair NK cell function in a dose- and time-dependent manner. In summary, this review provides an update on the effects of different novel molecules on the immune system focusing NK cells.

Sunitinib does not impair natural killer cell function in patients with renal cell carcinoma

“…The limitations of the current study include the small numbers of mRCC patients and controls. Nevertheless, the results suggest that treatment strategies involving NK cells, such as adoptive NK cell transfer (17,19), may potentially be used in combination with sunitinib and may offer a feasible treatment option for patients with mRCC in the future. Further trials are required to evaluate the effects of TKIs in larger cohorts.…”

“…Nevertheless, data are limited on how TKIs may interact with the immune system of an individual patient (16,19). The present study analyzed the influence of the TKI sunitinib on the cellular immunity of three patients with mRCC, focusing specifically on NK cell phenotype and functionality as potential targets for novel immunomodulatory treatment options.…”

“…Within the last two decades, numerous new strategies have been developed to improve overall survival, quality of life and disease regression in patients with advanced RCC (1,(4)(5)(6)16,19), and TKI therapy has been shown to be an important treatment modality in addressing these objectives (10,12,13). Nevertheless, data are limited on how TKIs may interact with the immune system of an individual patient (16,19).…”

“…NK cells are able to mediate antitumor effects and have thus been used for NK cell adoptive therapy in recent clinical trials (17). NK cells have further been reported as key players in TKI-mediated off-target effects on the immune system (18)(19)(20).…”

Inhibition of the Nkg2d Activating Receptor Expression on Cytotoxic Lymphocytes by Recombinant Mica Protein

“…Рядом авторов было показано, что протеоли-тический шеддинг белка MICA с поверхности опухолевых клеток с образованием sMICA может приводить к анергии эффекторных клеток за счет уменьшения поверхностной экспрессии активи-рующего рецептора NKG2D, что определяет ме-ханизм уклонения опухолевых клеток от иммун-ного надзора [10,13].…”