Tumor Immune Microenvironment for Effective Therapy II

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 7379

Special Issue Editor


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Guest Editor
Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
Interests: cancer biology; tumor microenvironment; inflammation; vascular biology; acidosis; pH sensing; G protein-coupled receptor; signal transduction
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Special Issue Information

Dear Colleagues,

Immunotherapy has changed the paradigm of cancer treatment and significantly improved clinical outcomes in a subset of cancer patients. However, the responses to immunotherapy and the therapeutic outcomes vary among cancer patients. Research demonstrates that the tumor microenvironment plays an important role in cancer immunotherapy. There are a variety of cell types, including cancer cells, T cells, B cells, natural killer cells, dendritic cells, tumor-associated macrophages, myeloid-derived suppressor cells, cancer-associated fibroblasts, and vascular cells, in the tumor microenvironment. Some of these cell types contribute to the immunosuppressive microenvironment in a tumor. Additionally, cytokines, chemokines, growth factors, and the extracellular matrix in the tumor microenvironment modulate immune cell functions and antitumor immunity. Moreover, the unique biochemical characteristics of the tumor microenvironment, such as hypoxia, acidosis, accumulation of lactate and adenosine, and nutrient deprivation, can be immune suppressive. A better understanding of the tumor immune microenvironment will be advantageous for developing effective cancer immunotherapy.

This Special Issue will cover research topics on tumor immune microenvironment and the implications in cancer immunotherapy, as indicated by, but not limited to, the keywords below. Original research papers, review articles, theories, and commentaries are all welcome.

Prof. Dr. Li Yang
Guest Editor

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Keywords

  • tumor microenvironment
  • cancer immunotherapy
  • immune checkpoints
  • immune cells
  • cancer-associated fibroblasts
  • vascular cells
  • inflammation
  • hypoxia
  • acidosis
  • cytokines

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Published Papers (4 papers)

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Research

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16 pages, 6036 KiB  
Article
Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion
by Yi-Ming Chang, Wen-Yen Huang, Shih-Hsien Yang, Chia-Ing Jan, Shin Nieh, Yaoh-Shiang Lin, Su-Feng Chen and Yu-Chun Lin
Cells 2024, 13(11), 968; https://doi.org/10.3390/cells13110968 - 3 Jun 2024
Viewed by 1078
Abstract
Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor [...] Read more.
Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment for Effective Therapy II)
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30 pages, 5293 KiB  
Article
Contemporaneous Perioperative Inflammatory and Angiogenic Cytokine Profiles of Surgical Breast, Colorectal, and Prostate Cancer Patients: Clinical Implications
by Leili Baghaie, Fiona Haxho, Fleur Leroy, Beth Lewis, Alexander Wawer, Shamano Minhas, William W. Harless and Myron R. Szewczuk
Cells 2023, 12(23), 2767; https://doi.org/10.3390/cells12232767 - 4 Dec 2023
Cited by 2 | Viewed by 1560
Abstract
Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgical [...] Read more.
Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgical breast, prostate, and colorectal cancer patients. Plasma samples were analyzed from 68 cancer patients who had not received treatment before surgery or adjuvant therapy until at least four weeks post-surgery. The levels of plasma cytokines, chemokines, and growth factors were simultaneously quantified and profiled using multiplexed immunoassays for eight time points sampled per patient. The immunologic processes are induced immediately after surgery in patients, characterized by a drastic short-term shift in the expression levels of pro-inflammatory and angiogenic molecules and cytokines. A rapid and significant spike in circulating plasma levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), placental growth factor (PLGF), and matrix metalloproteinase-9 (MMP-9) after surgery was noted. The rise in these molecules was concomitant with a significant drop in transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF-AB/BB), insulin-like growth factor-1 (IGF-1), and monocyte chemoattractant protein-2 (MCP-2). If not earlier, each plasma analyte was normalized to baseline levels within 1–2 weeks after surgery, suggesting that surgical intervention alone was responsible for these effects. The effects of surgical tumor removal on disrupting the pro-inflammatory and angiogenic plasma profiles of cancer patients provide evidence for potentiating malignant progression. Our findings indicate a narrow therapeutic window of opportunity after surgery to prevent disease recurrence. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment for Effective Therapy II)
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Review

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25 pages, 1865 KiB  
Review
Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity
by Nikolay K. Shakhpazyan, Liudmila M. Mikhaleva, Arkady L. Bedzhanyan, Zarina V. Gioeva, Alexander I. Mikhalev, Konstantin Y. Midiber, Valentina V. Pechnikova and Andrey E. Biryukov
Cells 2024, 13(17), 1437; https://doi.org/10.3390/cells13171437 - 27 Aug 2024
Viewed by 2265
Abstract
The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review [...] Read more.
The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the immune landscape within the tumor microenvironment. This review aims to elucidate the interactions between gut microbiota and tumor immune dynamics, with a focus on colorectal cancer (CRC). The review spans foundational concepts of immuno-microbial interplay, factors influencing microbiome composition, and evidence linking gut microbiota to cancer immunotherapy outcomes. Gut microbiota modulates anti-cancer immunity through several mechanisms, including enhancement of immune surveillance and modulation of inflammatory responses. Specific microbial species and their metabolic byproducts can significantly influence the efficacy of cancer immunotherapies. Furthermore, microbial diversity within the gut microbiota correlates with clinical outcomes in CRC, suggesting potential as a valuable biomarker for predicting response to immunotherapy. Conclusions: Understanding the relationship between gut microbiota and tumor immune responses offers potential for novel therapeutic strategies and biomarker development. The gut microbiota not only influences the natural history and treatment response of CRC but also serves as a critical modulator of immune homeostasis and anti-cancer activity. Further exploration into the microbiome’s role could enhance the effectiveness of existing treatments and guide the development of new therapeutic modalities. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment for Effective Therapy II)
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17 pages, 739 KiB  
Review
Interleukin-21 Influences Glioblastoma Course: Biological Mechanisms and Therapeutic Potential
by Alberto Repici, Alessio Ardizzone, Alessia Filippone, Cristina Colarossi, Marzia Mare, Gabriele Raciti, Deborah Mannino, Salvatore Cuzzocrea, Irene Paterniti and Emanuela Esposito
Cells 2023, 12(18), 2284; https://doi.org/10.3390/cells12182284 - 15 Sep 2023
Cited by 1 | Viewed by 1851
Abstract
Brain tumors represent a heterogeneous group of neoplasms involving the brain or nearby tissues, affecting populations of all ages with a high incidence worldwide. Among the primary brain tumors, the most aggressive and also the most common is glioblastoma (GB), a type of [...] Read more.
Brain tumors represent a heterogeneous group of neoplasms involving the brain or nearby tissues, affecting populations of all ages with a high incidence worldwide. Among the primary brain tumors, the most aggressive and also the most common is glioblastoma (GB), a type of glioma that falls into the category of IV-grade astrocytoma. GB often leads to death within a few months after diagnosis, even if the patient is treated with available therapies; for this reason, it is important to continue to discover new therapeutic approaches to allow for a better survival rate of these patients. Immunotherapy, today, seems to be one of the most innovative types of treatment, based on the ability of the immune system to counteract various pathologies, including cancer. In this context, interleukin 21 (IL-21), a type I cytokine produced by natural killer (NK) cells and CD4+ T lymphocytes, appears to be a valid target for new therapies since this cytokine is involved in the activation of innate and adaptive immunity. To match this purpose, our review deeply evaluated how IL-21 could influence the progression of GB, analyzing its main biological processes and mechanisms while evaluating the potential use of the latest available therapies. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment for Effective Therapy II)
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