Single-Cell Technologies to Decipher the Immune Microenvironment in Myeloid Neoplasms: Perspectives and Opportunities.

Chiara Caprioli,Chiara Caprioli,Chiara Caprioli,Pier Giuseppe Pelicci,Pier Giuseppe Pelicci,Iman Nazari,Iman Nazari,Sara Milovanovic

doi:10.3389/fonc.2021.796477

Abstract

Myeloid neoplasms (MN) are heterogeneous clonal disorders arising from the expansion of hematopoietic stem and progenitor cells. In parallel with genetic and epigenetic dynamics, the immune system plays a critical role in modulating tumorigenesis, evolution and therapeutic resistance at the various stages of disease progression. Single-cell technologies represent powerful tools to assess the cellular composition of the complex tumor ecosystem and its immune environment, to dissect interactions between neoplastic and non-neoplastic components, and to decipher their functional heterogeneity and plasticity. In addition, recent progress in multi-omics approaches provide an unprecedented opportunity to study multiple molecular layers (DNA, RNA, proteins) at the level of single-cell or single cellular clones during disease evolution or in response to therapy. Applying single-cell technologies to MN holds the promise to uncover novel cell subsets or phenotypic states and highlight the connections between clonal evolution and immune escape, which is crucial to fully understand disease progression and therapeutic resistance. This review provides a perspective on the various opportunities and challenges in the field, focusing on key questions in MN research and discussing their translational value, particularly for the development of more efficient immunotherapies.

Highlights

Myeloid neoplasms (MN) consist of a heterogeneous group of hematological cancers, arising from the hematopoietic stem cell (HSC) or progenitors in the bone marrow (BM) and sharing phenotypic features of the myeloid lineage [1]
Somatic mutations can be identified in the peripheral blood of healthy subjects, a phenomenon known as clonal hematopoiesis (CH) that reflects the expansion of mutated HSC; by years or decades, CH may evolve to acute myeloid leukemia (AML), eventually involving clinically recognizable pre-leukemic syndromes, such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) [5,6,7,8,9,10]
This review covers state-of-the-art single-cell technological applications with associated analysis methods; we aim to provide a perspective on the various opportunities to study the immune system and tumor microenvironment - for both experimental research and clinical translation - with a focus on specific issues relevant to MN

Summary

INTRODUCTION

Myeloid neoplasms (MN) consist of a heterogeneous group of hematological cancers, arising from the hematopoietic stem cell (HSC) or progenitors in the bone marrow (BM) and sharing phenotypic features of the myeloid lineage [1]. Thorsson et al [48] performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 cancer types, and identified six immune subtypes that span cancer tissue and molecular subtypes, and differ by somatic aberrations, microenvironment, and survival; results from this study are available for exploration through the interactive Cancer Research Institute iAtlas portal [49] Such resource is poorly applicable to MN research, as no MDS or MPN patients were included and limited data are available for AML, with no direct clues on tumor microenvironment composition, lymphocyte infiltration, immune features/modulators, immuno-oncology targets and associations with driver mutations [48]. This high-dimensional assay enables a more thorough characterization and higher resolution of cellular sub-populations and individual cells, which can be especially

Method

CONCLUSIONS