Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity.

The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19 CD138) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DRCD11bCD33 MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs.

The POD24 challenge: where do we go from here for early progressors?

Follicular lymphoma is the most common indolent lymphoma, with a favorable prognosis and survival measured in decades. However, approximately 15% to 20% of patients encounter early disease progression, termed POD24, within 24 months from diagnosis or treatment initiation. Recognizing the correlation between POD24 and a heightened risk of lymphoma-related death has sparked intensive investigations into the clinical and biological determinants of POD24 and the development of innovative treatment strategies targeting this group.

Unraveling the role of cancer-associated fibroblasts in B cell lymphoma.

Recent breakthroughs in research have sparked a paradigm shift in our understanding of cancer biology, uncovering the critical role of the crosstalk between tumor cells and the immune cells of the tumor microenvironment (TME) in malignant transformation. Fibroblasts have long been viewed as ancillary participants in cancer progression, often eclipsed by the prominence given to malignant cells. Novel investigations, however, have increasingly acknowledged the essential part played by the fibroblasts and their phenotypic doppelganger cancer-associated fibroblasts (CAFs) in fostering immunosuppression and promoting tumor progression.

Silencing GNAS enhances HDAC3i efficacy in CREBBP wild type B cell lymphoma.

The genetic era has opened the opportunity of using personalized therapeutic approaches, in part based on targeting genes with somatic mutations. For example, lymphomas harboring the highly recurrent CREBBP mutation show dependency on HDAC3, thus selective inhibition of HDAC3 reversed the epigenetic effects of CREBBP mutation, halted lymphoma growth, and induced MHC class II expression, enabling the T-cells to recognize and kill lymphoma cells. However, CREBBP wild type (WT) cells are less sensitive to this approach.

Multiomics analysis of IgM monoclonal gammopathies reveals epigenetic influence on oncogenesis via DNA methylation.

Currently, the role of DNA methylation in the immunoglobulin M (IgM) monoclonal gammopathy disease spectrum remains poorly understood. In the present study, a multiomics prospective analysis was conducted integrating DNA methylation, RNA sequencing (RNA-seq), and whole-exome sequencing data in 34 subjects (23 with Waldenström macroglobulinemia [WM], 6 with IgM monoclonal gammopathy of undetermined significance [MGUS], and 5 normal controls). Analysis was focused on defining differences between IgM gammopathies (WM/IgM-MGUS) compared with controls, and specifically between WM and IgM-MGUS.