Immune-Checkpoint Inhibitors in B-Cell Lymphoma

Abstract

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.

A Multi-scale, Multiomic Atlas of Human Normal and Follicular Lymphoma Lymph Nodes

“…Within the TME, T cells have been shown to express multiple immune checkpoint inhibitors in scRNA-seq datasets derived from FL patients (Andor et al, 2019). We also observed the enrichment of CD8+ T cells expressing several markers associated with T cell dysfunction and/or exhaustion including PDCD1 (PD-1), LAG3 , HAVCR2 ( TIM3 ), and CTLA4 (Armengol et al, 2021 ) . Interestingly, these CD8+ T cells also expressed molecules related to cytotoxic T cell function such as PRF1 , GZMA , and NKG7 (Ng et al, 2020; Szabo et al, 2019).…”

Enhanced clinical assessment of hematologic malignancies through routine paired tumor:normal sequencing

“…61 62 In contrast to solid tumors, hematologic malignancies tend to have lower levels of somatic mutation, 37 6 which may account for their relatively disappointing response to immune checkpoint inhibition. [63][64][65][66][67] . The unambiguous identification of somatic alterations via the use of a matched normal affords a more accurate assessment of TMB in these neoplasms.…”