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The Role of Tumor Microenvironment in the Pathogenesis and Progression...
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The Role of Tumor Microenvironment in the Pathogenesis and Progression of Hematological Malignancies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 6003

Special Issue Editor

Dr. Cesarina Giallongo

E-Mail Website
Guest Editor
Department of Medical, Surgical Sciences and Advanced Technologies G.F. Ingrassia, University of Catania, Catania, Italy
Interests: hematological malignancies; epigenetic; cancer; DNA repair; mitochondria and metabolism

Special Issue Information

Dear Colleagues,

The dynamic homeostasis typical of hematopoiesis is orchestrated by the bone marrow microenvironment, along with the hematopoietic system interaction, responding to different stress and damages. In this context, hematological malignant cells reshape the microenvironment to create a cancer-permissive niche, prompting tumor cell survival, proliferation, invasion, angiogenesis, drug resistance, and immune-escape. The latter is also mediated by the metabolic rewire typical of cancer cells, affecting the bone marrow microenvironment. For this reason, the tumor niche represents a bona-fide sanctuary site for malignant cells, due to the secretion of growth factors, pro-angiogenic molecules and direct interactions involving several surface proteins. Unravelling the signaling pathways by which tumor cells corrupt their microenvironment might lead to new opportunities to understand how to target the tumor niche, possibly improving the current therapies with new pharmacological strategies directed toward the eradication of tumor cells.

In the current Special Issue, we will discuss the major advances in the knowledge of cancer cells and the bone marrow niche, also focusing on the immune/non-immune interactions that contribute to the pathogenesis and progression of hematological malignancies.

Dr. Cesarina Giallongo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • inflammation
  • metabolic rewiring
  • epigenetics
  • mesenchymal stromal cells
  • immune cells
  • immune-escape

Published Papers (3 papers)

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Review

22 pages, 2489 KiB  
Review
Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers
by Sebastiano Giallongo, Andrea Duminuco, Ilaria Dulcamare, Tatiana Zuppelli, Enrico La Spina, Grazia Scandura, Annalisa Santisi, Alessandra Romano, Francesco Di Raimondo, Daniele Tibullo, Giuseppe A. Palumbo and Cesarina Giallongo
Biomolecules 2023, 13(12), 1701; https://doi.org/10.3390/biom13121701 - 24 Nov 2023
Viewed by 1190
Abstract
Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have [...] Read more.
Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in recent years as key regulators of the tumor microenvironment. Indeed, they are now considered active players in the pathophysiology of hematologic malignancies rather than passive bystanders in the hematopoietic microenvironment. Once a malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progression. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been shown that stromal cells themselves play a major role in several hematological malignancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterparts and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining the unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt tumor/MSC coupling. The present review focuses on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer progression. Full article
(This article belongs to the Special Issue The Role of Tumor Microenvironment in the Pathogenesis and Progression of Hematological Malignancies)
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36 pages, 5938 KiB  
Review
Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma
by Niyati Seshagiri Sharma and Bibha Choudhary
Biomolecules 2023, 13(11), 1629; https://doi.org/10.3390/biom13111629 - 07 Nov 2023
Viewed by 1730
Abstract
Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute [...] Read more.
Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. The review describes the role of BMME components in MM development and ongoing clinical trials using immunotherapeutic approaches. Full article
(This article belongs to the Special Issue The Role of Tumor Microenvironment in the Pathogenesis and Progression of Hematological Malignancies)
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34 pages, 2973 KiB  
Review
The Role of Extracellular Vesicles in the Pathogenesis of Hematological Malignancies: Interaction with Tumor Microenvironment; a Potential Biomarker and Targeted Therapy
by Kaushik Das, Tanmoy Mukherjee and Prem Shankar
Biomolecules 2023, 13(6), 897; https://doi.org/10.3390/biom13060897 - 27 May 2023
Cited by 5 | Viewed by 2699
Abstract
The tumor microenvironment (TME) plays an important role in the development and progression of hematological malignancies. In recent years, studies have focused on understanding how tumor cells communicate within the TME. In addition to several factors, such as growth factors, cytokines, extracellular matrix [...] Read more.
The tumor microenvironment (TME) plays an important role in the development and progression of hematological malignancies. In recent years, studies have focused on understanding how tumor cells communicate within the TME. In addition to several factors, such as growth factors, cytokines, extracellular matrix (ECM) molecules, etc., a growing body of evidence has indicated that extracellular vesicles (EVs) play a crucial role in the communication of tumor cells within the TME, thereby contributing to the pathogenesis of hematological malignancies. The present review focuses on how EVs derived from tumor cells interact with the cells in the TME, such as immune cells, stromal cells, endothelial cells, and ECM components, and vice versa, in the context of various hematological malignancies. EVs recovered from the body fluids of cancer patients often carry the bioactive molecules of the originating cells and hence can be considered new predictive biomarkers for specific types of cancer, thereby also acting as potential therapeutic targets. Here, we discuss how EVs influence hematological tumor progression via tumor–host crosstalk and their use as biomarkers for hematological malignancies, thereby benefiting the development of potential therapeutic targets. Full article
(This article belongs to the Special Issue The Role of Tumor Microenvironment in the Pathogenesis and Progression of Hematological Malignancies)
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