Myelopoiesis, metabolism and therapy: a crucial crossroads in cancer progression.

Antonio Sica,Alessandra Gennari,Valentina Guarneri

doi:10.15698/cst2019.09.197

Abstract

Cancers promote immunological stresses that induce alterations of the myelopoietic output, defined as emergency myelopoiesis, which lead to the generation of different myeloid populations endowed with tumor-promoting activities. New evidence indicates that acquisition of this tumor-promoting phenotype by myeloid cells is the result of a multistep process, encompassing initial events originating into the bone marrow and later steps operating in the tumor microenvironment. The careful characterization of these sequential mechanisms is likely to offer new potential therapeutic opportunities. Here, we describe relevant mechanisms of myeloid cells reprogramming that instate immune dysfunctions and limit effective responses to anticancer therapy and discuss the influence that metabolic events, as well as chemotherapy, elicit on such events.

Highlights

The bone marrow (BM) is a primary lymphoid organ that hosts hematopoietic progenitors and presides over hematopoiesis, which is defined as the production of all types of blood cells
New evidence indicates that acquisition of this tumor-promoting phenotype by myeloid cells is the result of a multistep process, encompassing initial events originating into the bone marrow and later steps operating in the tumor microenvironment
We reported that the macrophage colony-stimulating factor (M-CSF) elevates the myeloid cell levels of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway, which acts as negative regulator of the CXCR4 retention axis of hematopoietic cells in the BM [27], promoting mobilization of myeloid cells to periphery

Summary

Introduction

The bone marrow (BM) is a primary lymphoid organ that hosts hematopoietic progenitors and presides over hematopoiesis, which is defined as the production of all types of blood cells. Accumulation of myeloid progenitors and their differentiation to TAMs and MDSCs is the result of a process driven by cancer-related inflammation [25], involving: altered myelopoiesis; mobilization of myeloid precursors from the BM to periphery; recruitment of MDSCs and TAMs precursors into both secondary lymphoid organs and/or tumor tissues; functional diversion of myeloid cells in response to microenvironmental signals.

Results

Conclusion