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Cancers
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Tumor Immune Microenvironment in Gastric Cancers
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Tumor Immune Microenvironment in Gastric Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 25 December 2024 | Viewed by 5687

Special Issue Editors

Dr. Chandrani Sarkar

E-Mail Website
Guest Editor
Department of Pathology, University of South Alabama, Mobile, AL 36617, USA
Interests: gastrointestinal; stomach and colon; tumor microenvironment; neurohormones; neuropeptides
Dr. Debanjan Chakroborty

E-Mail Website
Guest Editor
Department of Pathology, University of South Alabama, Mobile, AL 36617, USA
Interests: tumor biology; tumor microenvironment; tumor metastasis; angiogenesis; targeted therapy; therapeutic resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastric cancer is one of the most common and deadly digestive tract malignancies worldwide. It represents the fifth most common cancer type and the fourth leading cause of cancer-related mortality in the world. The prognosis for patients with advanced gastric cancer is extremely poor, with a five-year overall survival rate of approximately 6% when diagnosed at advanced stages. Over the past decades, it has been increasingly evident that the tumor microenvironment (TME), which comprises of cellular and non-cellular components like the extracellular matrix, fibroblasts, immune cells, and endothelial cells that interact with proliferating tumor cells, plays a crucial role in gastric cancer progression by creating an environment that is conducive to the survival of the cancer cells. The TME also facilitates the escape of cancer cells from host immune surveillance. The aim of this Special Issue is to collect original articles and reviews that aid to improve the understanding of the role of the tumor immune microenvironment in gastric cancer. This includes, but is not limited to, the roles of tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), dendritic cells and myeloid-derived suppressor cells in the progression of gastric cancer and the possibilities of targeting these cells in gastric cancer.

Dr. Chandrani Sarkar
Dr. Debanjan Chakroborty
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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 immune microenvironment
  • gastric cancer
  • therapeutic strategies
  • therapeutic response
  • tumor-associated macrophages

Published Papers (4 papers)

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Research

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23 pages, 4125 KiB  
Article
Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis
by Georgios Konstantis, Georgia Tsaousi, Chryssa Pourzitaki, Stefan Kasper-Virchow, Gregor Zaun, Elisavet Kitsikidou, Moritz Passenberg, Vasilis Spyridon Tseriotis, Katharina Willuweit, Hartmut H. Schmidt and Jassin Rashidi-Alavijeh
Cancers 2024, 16(7), 1280; https://doi.org/10.3390/cancers16071280 - 26 Mar 2024
Viewed by 598
Abstract
Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain [...] Read more.
Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Results: Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Conclusion: Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment in Gastric Cancers)
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15 pages, 5649 KiB  
Article
Differences in the Tumor Microenvironment of EBV-Associated Gastric Cancers Revealed Using Single-Cell Transcriptome Analysis
by Mikhail Y. Salnikov, Gregory J. Fonseca and Joe S. Mymryk
Cancers 2023, 15(12), 3178; https://doi.org/10.3390/cancers15123178 - 14 Jun 2023
Cited by 1 | Viewed by 1501
Abstract
Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with nearly 10% of gastric cancers (GCs). These EBV-associated GCs (EBVaGCs) are molecularly, histopathologically, and clinically distinct from EBV-negative GCs (EBVnGCs). While viral genes in EBVaGCs contribute to the carcinogenesis process, viral proteins also represent foreign [...] Read more.
Epstein–Barr virus (EBV) is a gamma-herpesvirus associated with nearly 10% of gastric cancers (GCs). These EBV-associated GCs (EBVaGCs) are molecularly, histopathologically, and clinically distinct from EBV-negative GCs (EBVnGCs). While viral genes in EBVaGCs contribute to the carcinogenesis process, viral proteins also represent foreign antigens that could trigger enhanced immune responses compared to EBVnGCs. Despite prior investigations of the EBVaGC tumor microenvironment (TME), the cellular composition has not been thoroughly explored. In this study, cellular subpopulations overrepresented in EBVaGCs were identified and molecularly characterized. Genes consistently expressed across both bulk tumor and single-cell RNA sequencing data were highlighted, with the expression across the identified cellular subpopulations analyzed. As expected, based on existing histopathological analysis, EBVaGC is characterized by abundant lymphocytic infiltration of the stroma. Our molecular analysis identified three unique immune cell subpopulations in EBVaGC: T and B cells expressing high levels of proliferation markers and B cells expressing T cell features. The proliferating T cell cluster also expressed markers of follicular T helper cells. Overall, EBVaGC also exhibited unique features indicative of a higher inflammatory response. These substantial differences within the TME suggest that further detailed exploration of the cellular composition of EBVaGCs is needed, which may identify cellular subpopulations and phenotypes associated with patient outcomes. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment in Gastric Cancers)
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Review

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17 pages, 727 KiB  
Review
Therapeutic Immunomodulation in Gastric Cancer
by Venu Akkanapally, Xue-Feng Bai and Sujit Basu
Cancers 2024, 16(3), 560; https://doi.org/10.3390/cancers16030560 - 28 Jan 2024
Viewed by 2139
Abstract
Gastric carcinoma, being one of the most prevalent types of solid tumors, has emerged as the third leading cause of death worldwide. The symptoms of gastric cancer (GC) are typically complex, which makes early detection challenging. Immune checkpoint inhibition has become the new [...] Read more.
Gastric carcinoma, being one of the most prevalent types of solid tumors, has emerged as the third leading cause of death worldwide. The symptoms of gastric cancer (GC) are typically complex, which makes early detection challenging. Immune checkpoint inhibition has become the new standard targeted therapy for advanced or metastatic GC. It is currently being explored in various combinations, both with and without chemotherapy, across multiple therapies in clinical trials. Immunotherapy can stimulate immune responses in GC patients, leading to the destruction of cancer cells. Compared with traditional therapies, immunotherapy has shown strong effectiveness with tolerable toxicity levels. Hence, this innovative approach to the treatment of advanced GC has gained popularity. In this review, we have outlined the recent advancements in immunotherapy for advanced GC, including immune checkpoint inhibitors, cancer vaccines, vascular endothelial growth factor-A inhibitors, and chimeric antigen receptor T-cell therapy. Our current emphasis is on examining the immunotherapies presently employed in clinical settings, addressing the existing challenges associated with these therapeutic approaches, and exploring promising strategies to overcome their limitations. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment in Gastric Cancers)
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14 pages, 1270 KiB  
Review
TAMs and PD-1 Networking in Gastric Cancer: A Review of the Literature
by Melina Yerolatsite, Nanteznta Torounidou, Aristeidis Gogadis, Fani Kapoulitsa, Panagiotis Ntellas, Evangeli Lampri, Maria Tolia, Anna Batistatou, Konstantinos Katsanos and Davide Mauri
Cancers 2024, 16(1), 196; https://doi.org/10.3390/cancers16010196 - 30 Dec 2023
Viewed by 1042
Abstract
Background: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The [...] Read more.
Background: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). Aim of the study: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. Methods: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. Results: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. Conclusions: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment in Gastric Cancers)
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