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Advanced Research on the Immune Microenvironment in Tumors

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

Deadline for manuscript submissions: 20 February 2025 | Viewed by 5576

Special Issue Editor


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Guest Editor
1. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK
2. Cellular Pathology, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK
Interests: breast cancer; molecular pathology; prediction and prognosis; tumor microenvironment; hormone receptors; HER2; PD-L1

Special Issue Information

Dear Colleagues,

The interplay between tumor cells and the immune cells of the host is key in determining the development and progression of various types of cancers. Molecular research into the composition, topography and colocalization of the immune cells in the tumor microenvironment is thus critical to inform prognosis and suitability for immunotherapy.

The aim of this Special Issue is to bring investigators up to date with recent developments in research on the tumor microenvironment and its clinical implications. We invite original research and review articles into tumor microenvironment profiling. IJMS focuses on molecular studies in biology and chemistry, with a strong emphasis on molecular biology and molecular medicine, and we particularly welcome publications in molecular-level research. 

Prof. Dr. Abeer Shaaban
Guest Editor

Manuscript Submission Information

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Keywords

  • cancer
  • tumor microenvironment
  • TILs
  • tumor-associated macrophages
  • PD-L1

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Published Papers (3 papers)

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Research

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15 pages, 3158 KiB  
Article
Profiling of Tumour-Infiltrating Lymphocytes and Tumour-Associated Macrophages in Ovarian Epithelial Cancer—Relation to Tumour Characteristics and Impact on Prognosis
by Annabel Stout, Natalya Facey, Anjali Bhatnagar, Kirstie Rice, Fedor Berditchevski, Daniel Kearns, Amy Metcalf, Alaa Elghobashy and Abeer M. Shaaban
Int. J. Mol. Sci. 2024, 25(8), 4524; https://doi.org/10.3390/ijms25084524 - 20 Apr 2024
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Abstract
Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse [...] Read more.
Early evidence suggests a strong impact of tumour-infiltrating lymphocytes (TILs) on both the prognosis and clinical behaviour of ovarian cancer. Proven associations, however, have not yet translated to successful immunotherapies and further work in the field is urgently needed. We aimed to analyse the tumour microenvironment of a well-characterised cohort of ovarian cancer samples. Tumour markers were selected owing to their comparative underrepresentation in the current literature. Paraffin-embedded, formalin-fixed tumour tissue blocks of 138 patients representative of the population and including early stage disease were identified, stained for CD3, CD20, CD68 and CD163 and analysed for both the stromal and intertumoral components. Data were statistically analysed in relation to clinical details, histological subtype, borderline vs. malignant status, survival and management received. Mean stromal CD3, total CD3 count, mean stromal CD20 and total CD20 count all correlated negatively with survival. Malignant ovarian tumours consistently demonstrated significantly higher infiltration of all analysed immune cells than borderline tumours. Assessment of the stromal compartment produced a considerably higher proportion of significant results when compared to the intra-tumoural infiltrates. Customary assessment of solely intra-tumoural cells in advanced stage disease patients undergoing primary debulking surgery should be challenged, with recommendations for future scoring systems provided. Full article
(This article belongs to the Special Issue Advanced Research on the Immune Microenvironment in Tumors)
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24 pages, 8832 KiB  
Article
Comprehensive Analysis of Lung Adenocarcinoma and Brain Metastasis through Integrated Single-Cell Transcriptomics
by Vanessa G. P. Souza, Nikita Telkar, Wan L. Lam and Patricia P. Reis
Int. J. Mol. Sci. 2024, 25(7), 3779; https://doi.org/10.3390/ijms25073779 - 28 Mar 2024
Viewed by 2274
Abstract
Lung adenocarcinoma (LUAD) is a highly prevalent and lethal form of lung cancer, comprising approximately half of all cases. It is often diagnosed at advanced stages with brain metastasis (BM), resulting in high mortality rates. Current BM management involves complex interventions and conventional [...] Read more.
Lung adenocarcinoma (LUAD) is a highly prevalent and lethal form of lung cancer, comprising approximately half of all cases. It is often diagnosed at advanced stages with brain metastasis (BM), resulting in high mortality rates. Current BM management involves complex interventions and conventional therapies that offer limited survival benefits with neurotoxic side effects. The tumor microenvironment (TME) is a complex system where cancer cells interact with various elements, significantly influencing tumor behavior. Immunotherapies, particularly immune checkpoint inhibitors, target the TME for cancer treatment. Despite their effectiveness, it is crucial to understand metastatic lung cancer and the specific characteristics of the TME, including cell–cell communication mechanisms, to refine treatments. Herein, we investigated the tumor microenvironment of brain metastasis from lung adenocarcinoma (LUAD-BM) and primary tumors across various stages (I, II, III, and IV) using single-cell RNA sequencing (scRNA-seq) from publicly available datasets. Our analysis included exploring the immune and non-immune cell composition and the expression profiles and functions of cell type-specific genes, and investigating the interactions between different cells within the TME. Our results showed that T cells constitute the majority of immune cells present in primary tumors, whereas microglia represent the most dominant immune cell type in BM. Interestingly, microglia exhibit a significant increase in the COX pathway. Moreover, we have shown that microglia primarily interact with oligodendrocytes and endothelial cells. One significant interaction was identified between DLL4 and NOTCH4, which demonstrated a relevant association between endothelial cells and microglia and between microglia and oligodendrocytes. Finally, we observed that several genes within the HLA complex are suppressed in BM tissue. Our study reveals the complex molecular and cellular dynamics of BM-LUAD, providing a path for improved patient outcomes with personalized treatments and immunotherapies. Full article
(This article belongs to the Special Issue Advanced Research on the Immune Microenvironment in Tumors)
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Review

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19 pages, 2500 KiB  
Review
The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma
by Nan Hu, Haiyang Li, Changcheng Tao, Ting Xiao and Weiqi Rong
Int. J. Mol. Sci. 2024, 25(11), 5584; https://doi.org/10.3390/ijms25115584 - 21 May 2024
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Abstract
As one of the emerging hallmarks of tumorigenesis and tumor progression, metabolic remodeling is common in the tumor microenvironment. Hepatocellular carcinoma (HCC) is the third leading cause of global tumor-related mortality, causing a series of metabolic alterations in response to nutrient availability and [...] Read more.
As one of the emerging hallmarks of tumorigenesis and tumor progression, metabolic remodeling is common in the tumor microenvironment. Hepatocellular carcinoma (HCC) is the third leading cause of global tumor-related mortality, causing a series of metabolic alterations in response to nutrient availability and consumption to fulfill the demands of biosynthesis and carcinogenesis. Despite the efficacy of immunotherapy in treating HCC, the response rate remains unsatisfactory. Recently, research has focused on metabolic reprogramming and its effects on the immune state of the tumor microenvironment, and immune response rate. In this review, we delineate the metabolic reprogramming observed in HCC and its influence on the tumor immune microenvironment. We discuss strategies aimed at enhancing response rates and overcoming immune resistance through metabolic interventions, focusing on targeting glucose, lipid, or amino acid metabolism, as well as systemic regulation. Full article
(This article belongs to the Special Issue Advanced Research on the Immune Microenvironment in Tumors)
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