Abstract
In the era of novel agents and immunotherapies in solid and liquid tumors, there is an emerging need to understand the cross-talk between the neoplastic cells, the host immune system, and the microenvironment to mitigate proliferation, survival, migration and resistance to drugs. In the microenvironment of hematological tumors there are cells belonging to the normal bone marrow, extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and neoplastic cells themselves. In this context, myeloid suppressor cells are an emerging sub-population of regulatory myeloid cells at different stages of differentiation involved in cancer progression and chronic inflammation. In this review, monocytic myeloid derived suppressor cells and their potential clinical implications are discussed to give a comprehensive vision of their contribution to lymphoproliferative and myeloid disorders.
Highlights
With the nomenclature of myeloid derived suppressor cells (MDSCs) we identify a heterogeneous population of immature and mature cells of myeloid origin able to elicit T-cell anergy, promoting tumour immune-escape, via several mechanisms that include depletion of tryptophan, arginine, and cysteine due to the high expression level respectively of 2,3 indoleamine dioxygenase (IDO-1) and arginase (Arg-1), nytrosylation of T-cell receptor, and increased production and release of reactive oxygen species (ROS) [1,2,3]
In our Institution, from 2014 through 2016, we evaluated 375 patients with hematological malignancies (Figure 1); mo-MDSCs were identified as CD45+CD33+CD15-CD14+HLA-DR- in peripheral blood according to our internal procedure previously described [19,20], and we found that in comparison with a pool of 45 healthy subjects, mo-MDSCs were increased in all newly-diagnosed patients tested, except those affected by Waldenstrom disease
The highest percentages of mo-MDSCs was detectable in patients carrying mantle cell lymphoma and chronic lymphatic leukemia, while patients with Hodgkin lymphoma (HL), follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBLC) had comparable percentages, with widespread values associated to advanced stage
Summary
With the nomenclature of myeloid derived suppressor cells (MDSCs) we identify a heterogeneous population of immature and mature cells of myeloid origin able to elicit T-cell anergy, promoting tumour immune-escape, via several mechanisms that include depletion of tryptophan, arginine, and cysteine due to the high expression level respectively of 2,3 indoleamine dioxygenase (IDO-1) and arginase (Arg-1), nytrosylation of T-cell receptor, and increased production and release of reactive oxygen species (ROS) [1,2,3]. In the era of immune-therapies in cancer, there is an increasing interest on how MDSC can re-shape the tumor microenvironment or distant sites, affecting T-cell function and numbers. In this manuscript, we will review the clinical impact of mo-MDSC expansion in hematological tumors, including lymphoma, myeloma, and myeloproliferative neoplasms for their impact on the outcome of patients undergoing immunotherapy.
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