Immune Checkpoint Inhibitors to Treat Malignant Lymphomas

Abstract

Genetic and/or epigenetic changes provide antigen-derived diversity in neoplastic cells. Beside, these cells do not initiate immune response of host organisms. A variety of factors are responsible for the resistant to treatment, including individual variations in patients and somatic cell genetic differences in tumors, even those from the same tissue of origin. Immune system is controlled by several controlling mechanisms. Recently, a significant progress in hematologic treatment has been made; however, majority of diseases still remain incurable. Immunotherapy with checkpoint inhibitors has emerged as promising modality of antitumor treatment, showing marked response to several antigens, including cytotoxic T lymphocyte-associate protein-4 (CTLA-4) or programmed cell death 1 receptor (PD-1). In this review, we demonstrate actual knowledge on immune checkpoint function and its impact on development of new modality of antineoplastic treatment, using, for example, anti-CTLA-4 or PD-1/PD1 ligand (PD-L1) monoclonal antibodies in malignant lymphomas.

miR‐155expression in antitumor immunity: The higher the better?

“…Cancer cells, however, can evade antitumor responses of T cells by engaging inhibitory molecules normally involved in regulating the intensity of the immune response to pathogens and avoiding the development of autoimmunity (the so‐called immune checkpoints). The targeting of immune checkpoints, to impair the activation of signaling pathways aimed at decreasing T cell activation or proliferation, thus represents a promising strategy to increase the power of antitumor immunity without compromising its specificity or increasing morbidity (reviewed by References ). For example, mice vaccinated with irradiated B16 melanoma cells expressing GM‐Flt‐3 ligand that were also injected with a combination of antibodies directed against CTLA‐4 (cytotoxic T lymphocyte antigen‐4) and PD‐1 (programmed death‐1) rejected most of 3‐days pre‐implanted B16‐BL6 melanomas.…”

“…10,109,110 Mfsd2a downregulation by miR-155 might well play a role in DS and AD dementia, taking into account that miR-155 is also upregulated in both these pathologies. aimed at decreasing T cell activation or proliferation, thus represents a promising strategy to increase the power of antitumor immunity without compromising its specificity or increasing morbidity (reviewed by References 114,115 ). For example, mice vaccinated with irradiated B16 melanoma cells expressing GM-Flt-3 ligand that were also injected with a combination of antibodies directed against CTLA-4 (cytotoxic T lymphocyte antigen-4) and PD-1 (programmed death-1) rejected most of 3-days pre-implanted B16-BL6 melanomas.…”

Management of Drug Resistance in Mantle Cell Lymphoma

“…Despite initial in vitro and in vivo evidence for PD-L1 inhibition as a mechanism for effective enhancement of the T-cell response and T-cell-mediated killing of primary cells from PD-L1+ MCL patients, early clinical studies have not validated this approach as a successful strategy to treat patients with MCL [166]. However, as PD-L1 upregulation observed in MCL-T cell cocultures could be counteracted by either BTK or PI3K inhibition using ibrutinib or duvelisib [165], the combination of PD-1 blockade with BCR pathway inhibitors could represent a very promising combination [167].…”

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas

“…Nivolumab, a completely humanized IgG4 anti-PD-1 mAB, is now approved for melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma. The activity of nivolumab in lymphoid malignancies has also been widely tested (60,61,66,68,77). Patients with recurrent B-cell NHL were treated at the identical schedule with dose escalation of 1-3 mg/kg of nivolumab.…”