Immune checkpoint blockade in lymphoid malignancies

Abstract

Malignant cells may subvert and escape endogenous host immune surveillance by up‐regulation of immune inhibitory signals known as immune checkpoints. These checkpoints are important therapeutic targets, and antibodies that block checkpoint signaling have shown remarkable efficacy in some solid tumors as well as in some refractory hematologic malignancies. In hematologic cancers, the mechanism of these checkpoints is complex, as the tumor and immune system are one and the same. In this review, we evaluate the biology of checkpoint inhibition, review the current data on its efficacy in lymphoid tumors, and explore uncertainties in the field, including those involving the precise mechanisms of action, the appropriate timing of therapy, and the differences in response rate between lymphoid tumor types.

Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells

“…Examples of these advances include inhibitors of the PI3K/mTOR pathway; 14, 15, 16 Bruton’s tyrosine kinase inhibitors, 17 immunomodulatory agents that have multiple effects on normal and malignant cells 18, 19, 20 and immune checkpoint inhibitors. 21 …”

Upregulation of TET Activity with Ascorbic Acid Induces Epigenetic Modulation of Lymphoma Cells

“…Examples of these advances include inhibitors of the PI3K/mTOR pathway; [14][15][16] Bruton's tyrosine kinase inhibitors, 17 immunomodulatory agents that have multiple effects on normal and malignant cells [18][19][20] and immune checkpoint inhibitors. 21 Targeting the DNA hypermethylation in lymphoma has to date been limited to inhibitors of the DNMT enzyme. Clozel et al 2 demonstrated in vitro that azacytidine could inhibit DNMT and sensitize lymphoma cells to standard chemotherapy agents.…”

Immune response in LPD during methotrexate administration (MTX-LPD) in rheumatoid arthritis patients

“…Tumor cognate ligands can engage cytotoxic T-lymphocyte associated protein 4 (CTLA-4) or programmed-death 1 (PD-1) on the surface of T cells, leading to the downregulation of T-cell function. 84,85 The association between immune checkpoints and development of MTX-LPD remains to be elucidated.…”