Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Tumor Microenvironment and Immune Response in Breast Cancer
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Tumor Microenvironment and Immune Response in Breast Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 11268

Special Issue Editors

Prof. Dr. Steven R. Post

E-Mail Website
Guest Editor
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Interests: macrophages; scavenger receptors; tumor microenvironment; breast cancer; inflammation; immuno-oncology; cell signaling
Dr. Behjatolah Monzavi-Karbassi

E-Mail Website
Guest Editor
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Interests: tumor-associated glycans; glycoimmunology; tumor vaccines; immunotherapy; breast cancer
Prof. Dr. Thomas J. Kelly

E-Mail Website
Guest Editor
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Interests: fibroblasts; extracellular matrix; tumor microenvironment; breast cancer; invasion; metastasis; macrophages; fibroblast activation protein

Special Issue Information

Dear Colleagues,

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality for women worldwide. In addition to the mutations that drive carcinogenesis, it is increasingly clear that the interactions between breast cancer cells and their microenvironment are critical determinants of tumor progression, patient prognosis, and response to therapy. These interactions modulate tumor-immune responses by suppressing the ability of immune cells to inhibit tumor growth. Unfortunately, despite substantial efforts, approaches aimed at enhancing anti-tumor immune responses and preventing immune suppression in breast cancer have had limited success. Although not completely understood, factors associated with the diminished effectiveness of such approaches in treating breast cancer include the development of immune tolerance, dormancy, and escape. Thus, developing more effective therapeutic strategies requires a better understanding of the molecular and cellular interactions in the microenvironment of breast tumors that modulate cellular and humoral immune responses. 

This Special Issue will highlight studies on how the interactions between cancer cells and their microenvironment regulate the immune response and contribute to breast cancer development, progression, and metastasis. We invite researchers to submit high-quality original research papers and comprehensive reviews on topics that include but are not limited to the following:

  • Identification of novel immune modulators in breast cancer;
  • Mechanisms of immune suppression in breast tumors;
  • The role of the breast tumor microenvironment in regulating immune cell activation and phenotype;
  • Novel models and experimental approaches to study the immune response in breast tumors;
  • Delineating heterotypic signaling pathways between breast cancer and stromal cells;
  • Immune escape, dormancy, and tolerance in breast tumors;
  • Development of novel immune-based therapeutic and preventive strategies for breast cancer.

Prof. Dr. Steven R. Post
Dr. Behjatolah Monzavi-Karbassi
Prof. Dr. Thomas J. Kelly
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • breast cancer
  • stromal cells
  • immune cells
  • fibroblasts
  • macrophages
  • extracellular matrix
  • immunotherapy
  • immune suppression
  • cancer vaccines
  • tumor-associated antigens
  • cytokines
  • chemokines
  • angiogenesis
  • tumor heterogeneity
  • mouse models of breast cancer
  • organoids
  • patient-derived breast tumor explants

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

4 pages, 158 KiB  
Editorial
The Tumor Microenvironment and Immune Response in Breast Cancer
by Behjatolah Monzavi-Karbassi, Thomas Kelly and Steven R. Post
Int. J. Mol. Sci. 2024, 25(2), 914; https://doi.org/10.3390/ijms25020914 - 11 Jan 2024
Viewed by 645
Abstract
The complex interactions between cancer cells and their surrounding microenvironment are fundamental in determining tumor progression, response to therapy, and, ultimately, patient prognosis [...] Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)

Research

Jump to: Editorial, Review

14 pages, 1979 KiB  
Article
A Therapeutic Vaccine Targeting Rat BORIS (CTCFL) for the Treatment of Rat Breast Cancer Tumors
by Dmitri Loukinov, Amanda Laust Anderson, Mikayel Mkrtichyan, Anahit Ghochikyan, Samuel Rivero-Hinojosa, Jo Tucker, Victor Lobanenkov, Michael G. Agadjanyan and Edward L. Nelson
Int. J. Mol. Sci. 2023, 24(6), 5976; https://doi.org/10.3390/ijms24065976 - 22 Mar 2023
Cited by 1 | Viewed by 1914
Abstract
Cancer testis antigens are ideal for tumor immunotherapy due to their testis-restricted expression. We previously showed that an immunotherapeutic vaccine targeting the germ cell-specific transcription factor BORIS (CTCFL) was highly effective in treating aggressive breast cancer in the 4T1 mouse model. Here, we [...] Read more.
Cancer testis antigens are ideal for tumor immunotherapy due to their testis-restricted expression. We previously showed that an immunotherapeutic vaccine targeting the germ cell-specific transcription factor BORIS (CTCFL) was highly effective in treating aggressive breast cancer in the 4T1 mouse model. Here, we further tested the therapeutic efficacy of BORIS in a rat 13762 breast cancer model. We generated a recombinant VEE-VRP (Venezuelan Equine Encephalitis-derived replicon particle) vector-expressing modified rat BORIS lacking a DNA-binding domain (VRP-mBORIS). Rats were inoculated with the 13762 cells, immunized with VRP-mBORIS 48 h later, and then, subsequently, boosted at 10-day intervals. The Kaplan–Meier method was used for survival analysis. Cured rats were re-challenged with the same 13762 cells. We demonstrated that BORIS was expressed in a small population of the 13762 cells, called cancer stem cells. Treatment of rats with VRP-BORIS suppressed tumor growth leading to its complete disappearance in up to 50% of the rats and significantly improved their survival. This improvement was associated with the induction of BORIS-specific cellular immune responses measured by T-helper cell proliferation and INFγ secretion. The re-challenging of cured rats with the same 13762 cells indicated that the immune response prevented tumor growth. Thus, a therapeutic vaccine against rat BORIS showed high efficacy in treating the rat 13762 carcinoma. These data suggest that targeting BORIS can lead to the elimination of mammary tumors and cure animals even though BORIS expression is detected only in cancer stem cells. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)
►▼ Show Figures

Figure 1

24 pages, 7988 KiB  
Article
Reactivity Graph Yields Interpretable IgM Repertoire Signatures as Potential Tumor Biomarkers
by Dilyan Ferdinandov, Viktor Kostov, Maya Hadzhieva, Velizar Shivarov, Peter Petrov, Assen Bussarsky and Anastas Dimitrov Pashov
Int. J. Mol. Sci. 2023, 24(3), 2597; https://doi.org/10.3390/ijms24032597 - 30 Jan 2023
Cited by 2 | Viewed by 2066
Abstract
Combining adaptive and innate immunity induction modes, the repertoire of immunoglobulin M (IgM) can reflect changes in the internal environment including malignancies. Previously, it was shown that a mimotope library reflecting the public IgM repertoire of healthy donors (IgM IgOme) can be mined [...] Read more.
Combining adaptive and innate immunity induction modes, the repertoire of immunoglobulin M (IgM) can reflect changes in the internal environment including malignancies. Previously, it was shown that a mimotope library reflecting the public IgM repertoire of healthy donors (IgM IgOme) can be mined for efficient probes of tumor biomarker antibody reactivities. To better explore the interpretability of this approach for IgM, solid tumor-related profiles of IgM reactivities to linear epitopes of actual tumor antigens and viral epitopes were studied. The probes were designed as oriented planar microarrays of 4526 peptide sequences (as overlapping 15-mers) derived from 24 tumor-associated antigens and 209 cancer-related B cell epitopes from 30 viral antigens. The IgM reactivity in sera from 21 patients with glioblastoma multiforme, brain metastases of other tumors, and non-tumor-bearing neurosurgery patients was thus probed in a proof-of-principle study. A graph representation of the binding data was developed, which mapped the cross-reactivity of the mixture of IgM (poly)specificities, delineating different antibody footprints in the features of the graph—neighborhoods and cliques. The reactivity graph mapped the major features of the IgM repertoire such as the magnitude of the reactivity (titer) and major cross-reactivities, which correlated with blood group reactivity, non-self recognition, and even idiotypic specificities. A correlation between an aspect of this image of the IgM IgOme, namely, small cliques reflecting rare self-reactivities and the capacity of subsets of the epitopes to separate the diagnostic groups studied was found. In this way, the graph representation helped the feature selection in its filtering step and provided reduced feature sets, which, after recursive feature elimination, produced a classifier containing 51 peptide reactivities separating the three diagnostic groups with an unexpected efficiency. Thus, IgM IgOme approaches to repertoire studies is greatly augmented when self/viral antigens are used and the data are represented as a reactivity graph. This approach is most general, and if it is applicable to tumors in immunologically privileged sites, it can be applied to any solid tumors, for instance, breast or lung cancer. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)
►▼ Show Figures

Figure 1

11 pages, 2852 KiB  
Article
VT68.2: An Antibody to Chondroitin Sulfate Proteoglycan 4 (CSPG4) Displays Reactivity against a Tumor-Associated Carbohydrate Antigen
by Bernice Nounamo, Fariba Jousheghany, Eric Robb Siegel, Steven R. Post, Thomas Kelly, Soldano Ferrone, Thomas Kieber-Emmons and Behjatolah Monzavi-Karbassi
Int. J. Mol. Sci. 2023, 24(3), 2506; https://doi.org/10.3390/ijms24032506 - 28 Jan 2023
Cited by 3 | Viewed by 2095
Abstract
The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. Therefore, the potential for off-tumor activity remains a serious concern [...] Read more.
The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. Therefore, the potential for off-tumor activity remains a serious concern when targeting CSPG4 therapeutically. Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. The functional assays demonstrated that VT68.2 inhibited cancer cell migration. These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

16 pages, 2816 KiB  
Review
Decoding the IL-33/ST2 Axis: Its Impact on the Immune Landscape of Breast Cancer
by Bojan Stojanovic, Nevena Gajovic, Milena Jurisevic, Milica Dimitrijevic Stojanovic, Marina Jovanovic, Ivan Jovanovic, Bojana S. Stojanovic and Bojan Milosevic
Int. J. Mol. Sci. 2023, 24(18), 14026; https://doi.org/10.3390/ijms241814026 - 13 Sep 2023
Cited by 3 | Viewed by 1106
Abstract
Interleukin-33 (IL-33) has emerged as a critical cytokine in the regulation of the immune system, showing a pivotal role in the pathogenesis of various diseases including cancer. This review emphasizes the role of the IL-33/ST2 axis in breast cancer biology, its contribution to [...] Read more.
Interleukin-33 (IL-33) has emerged as a critical cytokine in the regulation of the immune system, showing a pivotal role in the pathogenesis of various diseases including cancer. This review emphasizes the role of the IL-33/ST2 axis in breast cancer biology, its contribution to cancer progression and metastasis, its influence on the tumor microenvironment and cancer metabolism, and its potential as a therapeutic target. The IL-33/ST2 axis has been shown to have extensive pro-tumorigenic features in breast cancer, starting from tumor tissue proliferation and differentiation to modulating both cancer cells and anti-tumor immune response. It has also been linked to the resistance of cancer cells to conventional therapeutics. However, the role of IL-33 in cancer therapy remains controversial due to the conflicting effects of IL-33 in tumorigenesis and anti-tumor response. The possibility of targeting the IL-33/ST2 axis in tumor immunotherapy, or as an adjuvant in immune checkpoint blockade therapy, is discussed. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)
►▼ Show Figures

Figure 1

12 pages, 485 KiB  
Review
From Reductionistic Approach to Systems Immunology Approach for the Understanding of Tumor Microenvironment
by Nicholas Koelsch and Masoud H. Manjili
Int. J. Mol. Sci. 2023, 24(15), 12086; https://doi.org/10.3390/ijms241512086 - 28 Jul 2023
Cited by 1 | Viewed by 1156
Abstract
The tumor microenvironment (TME) is a complex and dynamic ecosystem that includes a variety of immune cells mutually interacting with tumor cells, structural/stromal cells, and each other. The immune cells in the TME can have dual functions as pro-tumorigenic and anti-tumorigenic. To understand [...] Read more.
The tumor microenvironment (TME) is a complex and dynamic ecosystem that includes a variety of immune cells mutually interacting with tumor cells, structural/stromal cells, and each other. The immune cells in the TME can have dual functions as pro-tumorigenic and anti-tumorigenic. To understand such paradoxical functions, the reductionistic approach classifies the immune cells into pro- and anti-tumor cells and suggests the therapeutic blockade of the pro-tumor and induction of the anti-tumor immune cells. This strategy has proven to be partially effective in prolonging patients’ survival only in a fraction of patients without offering a cancer cure. Recent advances in multi-omics allow taking systems immunology approach. This essay discusses how a systems immunology approach could revolutionize our understanding of the TME by suggesting that internetwork interactions of the immune cell types create distinct collective functions independent of the function of each cellular constituent. Such collective function can be understood by the discovery of the immunological patterns in the TME and may be modulated as a therapeutic means for immunotherapy of cancer. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)
►▼ Show Figures

Figure 1

12 pages, 672 KiB  
Review
Butyrophilins: Dynamic Regulators of Protective T Cell Immunity in Cancer
by Rinkee Kumari, Elaheh Sadat Hosseini, Kristen E. Warrington, Tyler Milonas and Kyle K. Payne
Int. J. Mol. Sci. 2023, 24(10), 8722; https://doi.org/10.3390/ijms24108722 - 13 May 2023
Cited by 1 | Viewed by 1675
Abstract
The efficacy of current immunotherapies remains limited in many solid epithelial malignancies. Recent investigations into the biology of butyrophilin (BTN) and butyrophilin-like (BTNL) molecules, however, suggest these molecules are potent immunosuppressors of antigen-specific protective T cell activity in tumor beds. BTN and BTNL [...] Read more.
The efficacy of current immunotherapies remains limited in many solid epithelial malignancies. Recent investigations into the biology of butyrophilin (BTN) and butyrophilin-like (BTNL) molecules, however, suggest these molecules are potent immunosuppressors of antigen-specific protective T cell activity in tumor beds. BTN and BTNL molecules also associate with each other dynamically on cellular surfaces in specific contexts, which modulates their biology. At least in the case of BTN3A1, this dynamism drives the immunosuppression of αβ T cells or the activation of Vγ9Vδ2 T cells. Clearly, there is much to learn regarding the biology of BTN and BTNL molecules in the context of cancer, where they may represent intriguing immunotherapeutic targets that could potentially synergize with the current class of immune modulators in cancer. Here, we discuss our current understanding of BTN and BTNL biology, with a particular focus on BTN3A1, and potential therapeutic implications for cancer. Full article
(This article belongs to the Special Issue Tumor Microenvironment and Immune Response in Breast Cancer)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop