Regulatory myeloid cells: an underexplored continent in B-cell lymphomas

Abstract

In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behind the myeloid signatures are still poorly understood in germinal center B-cell lymphomas. Herein, we describe the role and clinical relevance of myeloid cells in B-cell lymphoma and propose innovative approaches to decipher this complex cellular compartment. Indeed, characterization of this heterogeneous cell ecosystem has been largely accomplished with "low-resolution" approaches like morphological evaluation and immunohistochemistry, where cells are characterized using a few proteins and qualitative metrics. High-resolution, quantitative approaches, such as mass cytometry, are valuable to better understand myeloid cell diversity, functions, and to identify potential targets for novel therapies.

Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: A meta-analysis of 40 studies

“…Macrophages are repolarized toward an M2 anti-inflammatory phenotype by IL-10. 24,64,68,69 In particular, MDSCs impair natural killer cells by decreasing cytokines such as IFN-γ. This suppression of natural killer cells is cell-cell contact-dependent.…”

HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma

“…Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to the immunosuppressive tumor microenvironment and tumor progression in B-cell lymphomas (Betsch et al, 2018). In particular, MDSCs may suppress T cell functions via expressing PD-L1, secreting IL-10/TGF-β, inducing T regulatory (Treg) development and expansion, and depleting certain amino acids (Serafini et al, 2008;Azzaoui et al, 2016;Roussel et al, 2017). Increased MDSCs are observed in various B-cell lymphomas, including HL, DLBCL and follicular lymphoma (FL), which correlates with poor prognosis and overall survival of patients (Roussel et al, 2017;Betsch et al, 2018).…”

Hide or defend, the two strategies of lymphoma immune evasion: potential implications for immunotherapy

“…While their immunosuppressive properties are well established, only few mechanisms have been explored in lymphoma. 144 Immunosuppressive functions of MDSC include: i) secretion of immunomodulatory factors and Treg expansion; ii) modulation of amino-acid metabolism and decrease of T-cell proliferation; iii) oxidative stress; iv) inhibition of T- or NK-cell viability and homing into the lymph nodes; and v) induction of T-cell apoptosis. In B-cell lymphoma, MDSC are involved in T-cell defect through PDL-1 expression, IL-10 secretion, Treg expansion, and modulation of amino-acid metabolism.…”