T-cell dysfunction in CLL is mediated through expression of Siglec-10 ligands CD24 and CD52 on CLL cells.

Autologous T-cell-based therapies, such as chimeric antigen receptor (CAR) T-cell therapy, exhibit low success rates in chronic lymphocytic leukemia (CLL) and correlate with a dysfunctional T-cell phenotype observed in patients. Despite various proposed mechanisms of T-cell dysfunction in CLL, the specific CLL-derived factors responsible remain unidentified. This study aimed to investigate the mechanisms through which CLL cells suppress CAR T-cell activation and function.

Ectopic expression of cGAS in enhances STING-mediated IFN-β response in human macrophages and dendritic cells.

Background: Interferon (IFN)-β induction via activation of the stimulator of interferon genes (STING) pathway has shown promising results in tumor models. STING is activated by cyclic dinucleotides such as cyclic GMP-AMP dinucleotides with phosphodiester linkages 2'-5' and 3'-5' (cGAMPs), that are produced by cyclic GMP-AMP synthetase (cGAS). However, delivery of STING pathway agonists to the tumor site is a challenge.

Correction: van Bruggen et al. Overcoming the Hurdles of Autologous T-Cell-Based Therapies in B-Cell Non-Hodgkin Lymphoma. 2020, , 3837.

In the original article [...

Overcoming the Hurdles of Autologous T-Cell-Based Therapies in B-Cell Non-Hodgkin Lymphoma.

The next frontier towards a cure for B-cell non-Hodgkin lymphomas (B-NHL) is autologous cellular immunotherapy such as immune checkpoint blockade (ICB), bispecific antibodies (BsAbs) and chimeric antigen receptor (CAR) T-cells. While highly successful in various solid malignancies and in aggressive B-cell leukemia, this clinical success is often not matched in B-NHL. T-cell subset skewing, exhaustion, expansion of regulatory T-cell subsets, or other yet to be defined mechanisms may underlie the lack of efficacy of these treatment modalities.

Human CXCR5 PD-1 CD8 T cells in healthy individuals and patients with hematologic malignancies.

Immune checkpoint blockade (ICB) has revolutionized cancer therapy, but varying response rates illustrate the need for biomarkers of response. Studies in mice have identified a subset of CD8 T cells that is essential for response to PD-1 ICB. These CD8 T cells co-express CXCR5, PD-1 and Tcf1, and provide effector T cells upon PD-1 ICB.

Functional diversification of hybridoma-produced antibodies by CRISPR/HDR genomic engineering.

Hybridoma technology is instrumental for the development of novel antibody therapeutics and diagnostics. Recent preclinical and clinical studies highlight the importance of antibody isotype for therapeutic efficacy. However, since the sequence encoding the constant domains is fixed, tuning antibody function in hybridomas has been restricted.

Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8 T cells and impede CAR T-cell efficacy.

In chronic lymphocytic leukemia (CLL), acquired T-cell dysfunction impedes development of effective immunotherapeutic strategies, through as-yet unresolved mechanisms. We have previously shown that CD8 T cells in CLL exhibit impaired activation and reduced glucose uptake after stimulation. CD8 T cells in CLL patients are chronically exposed to leukemic B cells, which potentially impacts metabolic homeostasis resulting in aberrant metabolic reprogramming upon stimulation.

CD40 signaling instructs chronic lymphocytic leukemia cells to attract monocytes via the CCR2 axis.

Chronic lymphocytic leukemia (CLL) cells are provided with essential survival and proliferative signals in the lymph node microenvironment. Here, CLL cells engage in various interactions with bystander cells such as T cells and macrophages. Phenotypically distinct types of tumor infiltrating macrophages can either be tumor supportive (M2) or play a role in tumor immune surveillance (M1).