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Medicina
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The Role of TME in Cancer Treatment
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The Role of TME in Cancer Treatment

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6923

Special Issue Editors

Prof. Dr. Weilin Jin

E-Mail Website
Guest Editor
Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, China
Interests: neuroscience; cell biology; cancer research
Special Issues, Collections and Topics in MDPI journals
Dr. Mingzhu Jin

E-Mail Website
Guest Editor
School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Interests: tumor microenvironment; tumor metabolism; drug repurposing; organoids; hypoxic niche
Prof. Dr. Xingchun Gao

E-Mail Website
Guest Editor
1. Yale School of Medicine, Yale University, New Haven, CT 06520, USA
2. Institute of Basic Medicine Science, Xi'an Medical University, Xi'an 710021, China
Interests: brain tumor; cell death; immunotherapy; drug resistance; stem cells; nanomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The tumor microenvironment (TME) plays a critical role in cancer treatment. It is a complicated ecosystem full of heterogeneity and affects almost every aspect of cancer biology. TME can be divided into six specialized microenvironments, including hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. Each specialized microenvironment has a close crosstalk with each other. The close interactions of the TME with the whole organism and the effect of therapy on the whole body should also be taken into consideration. Over the past few decades, the development of new technologies has provided even greater insight into the dynamic changes that occur in the tumor microenvironment and has opened up new avenues for the development of targeted therapies. As our understanding of TME is updated, we become better equipped to treat cancer. Thus, in this Special Issue, we aim to obtain a deeper understanding of the participation of TME in cancer treatment. We sincerely welcome researchers working in this field to submit original research articles or reviews to this Special Issue of The Role of TME in Cancer Treatment, which include, but are not neccesarily limited to, topics that focus on the role of TME in cancer treatment, tools and models to study TME, and therapies targeting TME. 

Prof. Dr. Weilin Jin
Dr. Mingzhu Jin
Prof. Dr. Xingchun Gao
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. Medicina 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 2200 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

  • tumor microenvironment
  • specialized microenvironment
  • hypoxic niche
  • immune microenvironment
  • metabolism microenvironment
  • acidic niche
  • innervated niche
  • mechanical microenvironment

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Published Papers (3 papers)

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Research

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18 pages, 4568 KiB  
Article
Identification of Genes Associated with Prognosis and Immunotherapy Prediction in Triple-Negative Breast Cancer via M1/M2 Macrophage Ratio
by Jianyu Liu, Yuhan Deng, Zhuolin Liu, Xue Li, Mingxuan Zhang, Xin Yu, Tong Liu, Kexin Chen and Zhigao Li
Medicina 2023, 59(7), 1285; https://doi.org/10.3390/medicina59071285 - 11 Jul 2023
Viewed by 2174
Abstract
Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10–15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into [...] Read more.
Background and Objectives: Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, accounts for ap-proximately 10–15% of all breast cancer cases. Currently, there is no effective therapeutic target for TNBC. Tu-mor-associated macrophages (TAMs), which can be phenotypically classified into M1 and M2 subtypes, have been shown to influence the prognosis of various cancers, including ovarian cancer. This study aimed to investigate the role of M1/M2 macrophages in the TNBC tumor microenvironment (TME), with a focus on identifying prognostic genes and predicting immunotherapy response. Materials and Methods: The study employed the CIBERSORT algorithm to analyze immune cell expression in the TME. Genes associated with the M1/M2 macrophage ratio were identified using Pearson correlation analysis and used to classify patients into dis-tinct clusters. Dimensionality reduction techniques, including univariate Cox regression and Lasso, were applied to these genes. The expression of prognostic genes was validated through immunohistochemistry. Results: The study found a high prevalence of TAMs in the TME. Among the patient clusters, 109 differentially expressed genes (DEGs) were identified. Three significant DEGs (LAMP3, GZMB, and CXCL13) were used to construct the riskScores. The riskScore model effectively stratified patients based on mortality risk. Gene Set Enrichment Analysis (GSEA) associated the riskScore with several significant pathways, including mismatch repair, JAK/STAT3 signaling, VEGF signaling, antigen processing presentation, ERBB signaling, and P53 signaling. The study also predicted patient sensitivity to im-munotherapy using the riskScores. The expression of the three significant DEGs was validated through immunohisto-chemistry. Conclusions: The study concluded that the riskScore model, based on the M1/M2 macrophage ratio, is a valid prognostic tool for TNBC. The findings underscore the importance of the TME in TNBC progression and prognosis and highlight the po-tential of the riskScore model in predicting immunotherapy response in TNBC patients. Full article
(This article belongs to the Special Issue The Role of TME in Cancer Treatment)
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19 pages, 7351 KiB  
Article
A Novel Notch-Related Gene Signature for Prognosis and Immune Response Prediction in Ovarian Cancer
by Yanan Pi, Fusheng Sun, Zhaocong Zhang, Xiaoli Liu and Ge Lou
Medicina 2023, 59(7), 1277; https://doi.org/10.3390/medicina59071277 - 9 Jul 2023
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Abstract
Background and Objectives: Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role of Notch in ovarian cancer [...] Read more.
Background and Objectives: Notch is a fascinating signaling pathway. It is extensively involved in tumor growth, cancer stem cells, metastasis, and treatment resistance and plays important roles in metabolic regulation, tumor microenvironment, and tumor immunity. However, the role of Notch in ovarian cancer (OC) has yet to be fully understood. Therefore, this study systematically described the expression, mutation, and copy number variation of genes in the Notch signaling pathway in OC and evaluated the relationship between gene mutation and Overall Survival (OS) prognosis. Materials and Methods: Notch risk score (NTRS) was established by univariate Cox regression analysis combined with Lasso regression analysis, and the efficacy of NTRS in predicting prognosis and immunotherapy response in patients with OC was verified. We further assessed the correlations of NTRS with clinical features, immune infiltration level, immune checkpoint expression, and immune characteristics. Additionally, differential expression and functions of the fourteen signature genes were confirmed via vitro assays. Results: The results showed that Notch genes (NTGs) were markedly differentiated between tumor and normal tissues, which may help to explain the high heterogeneity in the biological characteristics and therapeutic outcomes of human OC. A Notch risk (NTR) prognostic model based on 11 key NTGs was successfully constructed. Tumors with high Notch risk scores (NTRS) were independently associated with shorter overall survival and poorer immunotherapy outcomes. We further assessed the correlations of NTRS with immune characteristics. The results showed that NTGs play a key role in regulating the tumor immune microenvironment. Additionally, we validated the baseline and induced expressions of 14 prognosis-related NTGs in our own OC samples. In vitro assays confirmed that the knockdown of NCOR2 and APH1B and overexpression of HEY2 and SKP2 could inhibit the proliferation, invasion, and migration of OC cells. Conclusions: These findings emphasize that Notch multilayer changes are associated with the prognosis of patients with OC and the characteristics of immune cell infiltration. Our predictive signature may predict the prognosis and immunotherapy response of OC patients in an independent manner. NCOR2, APH1B, HEY2, and SKP2 may more prominently represent important indicators to improve patient prognosis. Full article
(This article belongs to the Special Issue The Role of TME in Cancer Treatment)
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Review

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15 pages, 1870 KiB  
Review
Diapause-like Drug-Tolerant Persister State: The Key to Nirvana Rebirth
by Han-Lin Chen and Wei-Lin Jin
Medicina 2024, 60(2), 228; https://doi.org/10.3390/medicina60020228 - 28 Jan 2024
Viewed by 2073
Abstract
Cancer is one of the leading causes of death in the world. Various drugs have been developed to eliminate it but to no avail because a tumor can go into dormancy to avoid therapy. In the past few decades, tumor dormancy has become [...] Read more.
Cancer is one of the leading causes of death in the world. Various drugs have been developed to eliminate it but to no avail because a tumor can go into dormancy to avoid therapy. In the past few decades, tumor dormancy has become a popular topic in cancer therapy. Recently, there has been an important breakthrough in the study of tumor dormancy. That is, cancer cells can enter a reversible drug-tolerant persister (DTP) state to avoid therapy, but no exact mechanism has been found. The study of the link between the DTP state and diapause seems to provide an opportunity for a correct understanding of the mechanism of the DTP state. Completely treating cancer and avoiding dormancy by targeting the expression of key genes in diapause are possible. This review delves into the characteristics of the DTP state and its connection with embryonic diapause, and possible treatment strategies are summarized. The authors believe that this review will promote the development of cancer therapy. Full article
(This article belongs to the Special Issue The Role of TME in Cancer Treatment)
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