Immune-Checkpoint Blockade Therapy in Lymphoma

Abstract

Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with malignant lymphoma and their efficacy has been reported. For example, in Hodgkin lymphoma, immune-checkpoint blockade has resulted in response rates of 65% to 75%. However, in non-Hodgkin lymphoma, the response rate to immune-checkpoint blockade was lower. In this review, we evaluate the biology of immune-checkpoint inhibition and the current data on its efficacy in malignant lymphoma, and identify the cases in which the treatment was more effective.

A Phase 1b Study to Evaluate the Safety and Efficacy of Durvalumab in Combination With Tremelimumab or Danvatirsen in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

“…Immune checkpoint inhibitors, which enhance T-cell activation, have exhibited antitumor activity in preliminary studies within some lymphoma subtypes, principally classical Hodgkin lymphoma. [5][6][7][8] While the role of immune checkpoint proteins in the pathogenesis of DLBCL has not yet been fully elucidated, a recent meta-analysis indicated that high expression of programmed death-ligand 1 (PD-L1) was associated with poor prognosis in patients with DLBCL. 9 PD-L1 represents a potential therapeutic target in DLBCL; the anti-PD-L1 antibody durvalumab showed efficacy in patients with treatment-naïve DLBCL when administered in combination with R-CHOP.…”

Immune checkpoint inhibitors in lymphoma: challenges and opportunities

“…To discern the mechanism of action of ICIs, it is crucial to understand how the CTLA-4 and PD-1 ligands play a role in the immune response. CTLA-4 regulates T-cell proliferation early in an immune response, primarily in lymph nodes, whereas PD-1 suppresses T-cells later in an immune response, primarily in peripheral tissues (4). CTLA-4 works by indirectly diminishing signaling through its co-stimulatory receptor, CD28 (Figure 1).…”

Current Immunotherapy Approaches in Non-Hodgkin Lymphomas

“…Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) binds to CD80 (B7-1) or CD86 (B7-2) and decreases activity of T cells by interrupting CD28-mediated co-stimulatory signaling. Aberrant overexpression of programmed death ligands 1 and 2 (PD-L1, PD-L2) or T-cell immunoglobulin and mucin domain 3 (TIM3) on malignant cells induce T-cell impairment, exhaustion, and apoptosis [ 64 , 65 , 66 ]. With the approval of several immune checkpoint inhibitors for the treatment of diverse solid cancers, it is now evident that the original proof-of-concept of inhibition of cancer-induced immunosuppression successfully translated into clinical practice.…”