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Tumor Microenvironment: A Key Player in Cancer Growth
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Tumor Microenvironment: A Key Player in Cancer Growth

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

Deadline for manuscript submissions: closed (20 September 2022) | Viewed by 11051

Special Issue Editors

Prof. Dr. Rosa Di Liddo

E-Mail Website
Guest Editor
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
Interests: leukemia; skin cancers; adrenomedullin signaling; neuroinflammation; multipotent stem cells; S100B
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Adriano Venditti

E-Mail Website
Guest Editor
Hematology, Department of Biomedicine and Prevention, “Tor Vergata” University of Rome, Roma, Italy
Interests: AML; HSCT; MRD; novel agents; guidelines; ELN; genetics; cytogenetics; MDS; chemotherapy
Special Issues, Collections and Topics in MDPI journals
Dr. Giorgia Simonetti

E-Mail Website
Guest Editor
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, FC, Italy
Interests: acute myeloid leukemia; genomics; cell metabolism; targeted therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite numerous developments in medicine, tumors are still the leading cause of death in the world. In the last decade, several lines of evidence suggest that both cellular and acellular components in the tumor microenvironment (TME) affect cancer cell growth, invasiveness and response to therapies. Thus, understanding the dynamic functions and regulatory factors of TME could be useful to enhance the efficacy and selectivity of anticancer strategies. Therefore, authors are invited to submit original research articles or relevant topic reviews on specialized TME components that play critical roles in disease initiation, maintenance and relapse of solid tumors and hematologic malignancies.

Prof. Dr. Rosa Di Liddo
Prof. Dr. Adriano Venditti
Dr. Giorgia Simonetti
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

  • stromal cells
  • immune cells
  • cancer-associated fibroblasts (CAFs)
  • vascular and nervous factors and networks
  • extracellular matrix (ECM)
  • TME-targeting therapies

Published Papers (6 papers)

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Research

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20 pages, 3703 KiB  
Article
Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model
by Valentino Le Noci, Giancarla Bernardo, Giacomo Manenti, Gabriele Infante, Dariush Khaleghi Hashemian, Lucia Minoli, Simone Canesi, Francesca Bianchi, Tiziana Triulzi, Stefania Arioli, Loris De Cecco, Simone Guglielmetti, Federico Ambrogi, Camilla Recordati, Nicoletta Gagliano, Elda Tagliabue, Michele Sommariva and Lucia Sfondrini
Int. J. Mol. Sci. 2022, 23(21), 12748; https://doi.org/10.3390/ijms232112748 - 22 Oct 2022
Cited by 5 | Viewed by 1840
Abstract
An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin [...] Read more.
An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan–Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer. Full article
(This article belongs to the Special Issue Tumor Microenvironment: A Key Player in Cancer Growth)
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17 pages, 4017 KiB  
Article
Integrated Analyses of m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Infiltration Characterization in Pan-Cancer
by Qingkang Cao and Yuanyuan Chen
Int. J. Mol. Sci. 2022, 23(19), 11182; https://doi.org/10.3390/ijms231911182 - 23 Sep 2022
Cited by 1 | Viewed by 1578
Abstract
The invasion of immune cells in the tumor microenvironment (TME) is closely related to cancer development. Studies have demonstrated that N6-methyladenosine (m6A) can affect the invasion of immune cells in TME as well as cancer development. We comprehensively analyzed the RNA-seq [...] Read more.
The invasion of immune cells in the tumor microenvironment (TME) is closely related to cancer development. Studies have demonstrated that N6-methyladenosine (m6A) can affect the invasion of immune cells in TME as well as cancer development. We comprehensively analyzed the RNA-seq data of 16 different cancer types based on 20 m6A regulators and identified two distinct m6A modification patterns, which were closely associated with TME cell infiltration and overall patient survival. Then, we used principal component analysis (PCA) to construct m6Ascore based on the expression of m6A-related prognostic genes, which can successfully predict patient survival. The low-m6Ascore subtype is characterized by more immune cell infiltration, good prognosis and lower TNM stages, while the high-m6Ascore subtype is characterized by low immune infiltration, stromal activation, and poor prognosis. m6Ascore was also closely associated with immunotherapy response and was significantly higher in complete response/partial response (CR/PR) patients than in stable disease/progressive disease (SD/PD) patients in both immunotherapy cohorts. Therefore, our study indicates that m6A modification plays an important role in the prognosis of pan-cancer and the formation of complex TME in pan-cancer. Our research helps to improve the cognition of m6A modifications at pan-cancer levels and identify more effective strategies for immunotherapy. Full article
(This article belongs to the Special Issue Tumor Microenvironment: A Key Player in Cancer Growth)
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Review

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11 pages, 271 KiB  
Review
Measurable Residual Disease (MRD) as a Surrogate Efficacy-Response Biomarker in AML
by Elisa Meddi, Arianna Savi, Federico Moretti, Flavia Mallegni, Raffaele Palmieri, Giovangiacinto Paterno, Elisa Buzzatti, Maria Ilaria Del Principe, Francesco Buccisano, Adriano Venditti and Luca Maurillo
Int. J. Mol. Sci. 2023, 24(4), 3062; https://doi.org/10.3390/ijms24043062 - 04 Feb 2023
Cited by 6 | Viewed by 1728
Abstract
In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as [...] Read more.
In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal post-remission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint. Full article
(This article belongs to the Special Issue Tumor Microenvironment: A Key Player in Cancer Growth)
11 pages, 855 KiB  
Review
Choroidal Neovascular Membranes in Retinal and Choroidal Tumors: Origins, Mechanisms, and Effects
by Federico Di Staso, Mariachiara Di Pippo and Solmaz Abdolrahimzadeh
Int. J. Mol. Sci. 2023, 24(2), 1064; https://doi.org/10.3390/ijms24021064 - 05 Jan 2023
Cited by 4 | Viewed by 1469
Abstract
Choroidal neovascularizations are historically associated with exudative macular degeneration, nonetheless, they have been observed in nevus, melanoma, osteoma, and hemangioma involving the choroid and retina. This review aimed to elucidate the possible origins of neovascular membranes by examining in vivo and in vitro [...] Read more.
Choroidal neovascularizations are historically associated with exudative macular degeneration, nonetheless, they have been observed in nevus, melanoma, osteoma, and hemangioma involving the choroid and retina. This review aimed to elucidate the possible origins of neovascular membranes by examining in vivo and in vitro models compared to real clinical cases. Among the several potential mechanisms examined, particular attention was paid to histologic alterations and molecular cascades. Physical or biochemical resistance to vascular invasion from the choroid offered by Bruch’s membrane, the role of fibroblast growth factor 2 and vascular endothelial growth factor, resident or recruited stem-like/progenitor cells, and other angiogenic promoters were taken into account. Even if the exact mechanisms are still partially obscure, experimental models are progressively enhancing our understanding of neovascularization etiology. Choroidal neovascularization (CNV) over melanoma, osteoma, and other tumors is not rare and is not contraindicative of malignancy as previously believed. In addition, CNV may represent a late complication of either benign or malignant choroidal tumors, stressing the importance of a long follow-up. Full article
(This article belongs to the Special Issue Tumor Microenvironment: A Key Player in Cancer Growth)
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14 pages, 1043 KiB  
Review
γδ T Lymphocytes as a Double-Edged Sword—State of the Art in Gynecological Diseases
by Anna Pawłowska, Yelizaveta Natochina, Witold Zardzewiały, Wiktoria Skiba, Karolina Włodarczyk, Aleksandra Maciejczyk, Dorota Suszczyk and Iwona Wertel
Int. J. Mol. Sci. 2022, 23(23), 14797; https://doi.org/10.3390/ijms232314797 - 26 Nov 2022
Cited by 3 | Viewed by 1534
Abstract
Human gamma-delta (γδ) T cells are a heterogeneous cell population that bridges the gap between innate and acquired immunity. They are involved in a variety of immunological processes, including tumor escape mechanisms. However, by being prolific cytokine producers, these lymphocytes also participate in [...] Read more.
Human gamma-delta (γδ) T cells are a heterogeneous cell population that bridges the gap between innate and acquired immunity. They are involved in a variety of immunological processes, including tumor escape mechanisms. However, by being prolific cytokine producers, these lymphocytes also participate in antitumor cytotoxicity. Which one of the two possibilities takes place depends on the tumor microenvironment (TME) and the subpopulation of γδ T lymphocytes. The aim of this paper is to summarize existing knowledge about the phenotype and dual role of γδ T cells in cancers, including ovarian cancer (OC). OC is the third most common gynecological cancer and the most lethal gynecological malignancy. Anticancer immunity in OC is modulated by the TME, including by immunosuppressive cells, cytokines, and soluble factors. Immune cells are exposed in the TME to many signals that determine their immunophenotype and can manipulate their functions. The significance of γδ T cells in the pathophysiology of OC is enigmatic and remains to be investigated. Full article
(This article belongs to the Special Issue Tumor Microenvironment: A Key Player in Cancer Growth)
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20 pages, 17979 KiB  
Review
Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?
by Arianna Filippelli, Cinzia Del Gaudio, Vittoria Simonis, Valerio Ciccone, Andrea Spini and Sandra Donnini
Int. J. Mol. Sci. 2022, 23(21), 13401; https://doi.org/10.3390/ijms232113401 - 02 Nov 2022
Cited by 5 | Viewed by 2131
Abstract
Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in [...] Read more.
Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis. Full article
(This article belongs to the Special Issue Tumor Microenvironment: A Key Player in Cancer Growth)
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