NK and NKT Cell-Mediated Immune Surveillance against Hematological Malignancies

Abstract

Recent cancer treatment modalities have been intensively focused on immunotherapy. The success of chimeric antigen receptor T cell therapy for treatment of refractory B cell acute lymphoblastic leukemia has pushed forward research on hematological malignancies. Among the effector types of innate lymphocytes, natural killer (NK) cells show great importance in immune surveillance against infectious and tumor diseases. Particularly, the role of NK cells has been argued in either elimination of target tumor cells or escape of tumor cells from immune surveillance. Therefore, an NK cell activation approach has been explored. Recent findings demonstrate that invariant natural killer T (iNKT) cells capable of producing IFN-γ when optimally activated can promptly trigger NK cells. Here, we review the role of NKT and/or NK cells and their interaction in anti-tumor responses by highlighting how innate immune cells recognize tumors, exert effector functions, and amplify adaptive immune responses. In addition, we discuss these innate lymphocytes in hematological disorders, particularly multiple myeloma and acute myeloid leukemia. The immune balance at different stages of both diseases is explored in light of disease progression. Various types of innate immunity-mediated therapeutic approaches, recent advances in clinical immunotherapies, and iNKT-mediated cancer immunotherapy as next-generation immunotherapy are then discussed.

Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma

“…16e ). Most of the NKT cells were activated and strongly expressed the GZMB, GZMA, and IFNG genes 60 , indicating that they are performing tumor cytotoxicity activities in the OS (Fig. 7d ).…”

Immune Phenomena in Myeloid Neoplasms: An “Egg or Chicken” Question

“…Autoimmunity and immunodeficiency are a hallmark of CLL, with a relentless accumulation of anergic, selfreactive CD5+ B cells, which produce several polyreactive natural autoantibodies (76). As regards myeloid neoplasms, it may be hypothesized that natural autoantibodies may contribute (or not) to the first-line defense of innate immunity that has been found deficient in most of these disease (77)(78)(79).…”

Impact of MYC on Anti-Tumor Immune Responses in Aggressive B Cell Non-Hodgkin Lymphomas: Consequences for Cancer Immunotherapy

“…These results suggest that CAR T cell therapies might overcome the negative effects of MYC overexpression. Efficacy of novel CAR T cells targeting other antigens, such as CD22, CD30 and CD79b [ 176 , 177 , 178 , 179 , 180 , 181 ] and innate immunity-mediated CAR NK cells [ 182 ] on MYC overexpressing lymphomas are under investigation.…”