The Role of Immunity in the Tumor Microenvironment

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

Deadline for manuscript submissions: 15 July 2024 | Viewed by 4724

Special Issue Editor

La Jolla Institute for Immunology, California, CA, USA
Interests: cancer immunotherapy; immunology; cancer biomarkers; cancer biology; pharmacology & pharmacy; biochemistry & molecular biology; plant sciences research & experimental medicine

Special Issue Information

Dear Colleagues,

The tumor microenvironment (TME) is an intricate entity that varies between different tumor types and includes the interplay of different components, such as extracellular matrix, blood vessels, tumor cells, and immune cells. It is now well established that the tumor microenvironment plays a tremendous role in cancer progression and regulating therapeutic response. Of all the therapeutic modalities affected by the TME, immunotherapies are also influenced by the participation of different regulatory molecules from immune cells and components of the TME. The latest developments in the field of immunology have significantly improved the efficacy of diverse immunotherapies, such as monoclonal antibody (MAB) therapy, immune checkpoint blockade (ICB) therapy, vaccines, CAR-T therapy, etc., against cancer cells. However, the understanding of the immune system in the TME still requires an in-depth understanding as it is now well recognized that the presence of different innate and adaptive immune cells in the TME can provide both pro- and anti-tumorigenic immunity against cancer cells. Furthermore, recent studies have shown the presence of microbiota in the TME, and they can modulate the therapeutic response efficacy through the alterations of immunity against cancer cells. Therefore, a thorough knowledge of the role of immunity in the TME can have a great impact on increasing the efficacy of immunotherapeutic options in cancer treatment. Thus, this Special Issue invites manuscripts in the form of original research articles, reviews, etc., related to the role of immunity in the TME to ultimately broaden the understanding of how to target cancer cells efficiently.

Dr. Nand K Roy
Guest Editor

Manuscript Submission Information

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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 microenvironment
  • immunity
  • immunotherapy
  • microbiome
  • immune checkpoint blockade (ICB) therapy
  • vaccines
  • CAR-T therapy

Published Papers (3 papers)

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Research

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19 pages, 10074 KiB  
Article
Deciphering the Role of the Anaphylatoxin C3a: A Key Function in Modulating the Tumor Microenvironment
by Jolimar Hanna, Franck Ah-Pine, Chailas Boina, Yosra Bedoui, Philippe Gasque and Axelle Septembre-Malaterre
Cancers 2023, 15(11), 2986; https://doi.org/10.3390/cancers15112986 - 30 May 2023
Cited by 1 | Viewed by 1424
Abstract
The complement system plays a crucial role in cancer development. Our study investigated the role of C3a anaphylatoxin on the tumor microenvironment. Our models consisted of mesenchymal stem cells (MSC-like, 3T3-L1), macrophages (Raw 264.7 Blue, (RB)) and tumor cells (melanoma B16/F0). Recombinant mouse [...] Read more.
The complement system plays a crucial role in cancer development. Our study investigated the role of C3a anaphylatoxin on the tumor microenvironment. Our models consisted of mesenchymal stem cells (MSC-like, 3T3-L1), macrophages (Raw 264.7 Blue, (RB)) and tumor cells (melanoma B16/F0). Recombinant mouse (Mo) C3a (rC3a) was produced in CHO cells transfected with a Mo-IL10-signal peptide-Mo C3a plasmid construct. The effects of rC3a, IFN-γ, TGF-β1, and LPS were tested on the expression of C3, C3aR, PI3K, cytokines, chemokines, transcription factors, antioxidant defense mechanisms, angiogenesis and macrophage polarization (M1/M2). 3T3-L1 expressed the highest levels of C3, while C3aR was expressed more by RB. Interestingly, expression of C3/3T3-L1 and C3aR/RB was markedly upregulated by IFN-γ. rC3a was found to upregulate the expression of anti-inflammatory cytokines (IL-10) on 3T3-L1 and TGF-β1 on RB. rC3a also upregulated the expression of pro-inflammatory cytokines in RB. The expression of CCL-5 increased in 3T3-L1 in response to rC3a. On RB, rC3a did not alter M1/M2 polarization but upregulated the expression of antioxidant defense genes, HO-1, and VEGF. C3/C3a produced mainly by MSC may play a critical role in TME remodeling by stimulating both anti-inflammatory and proangiogenic activities of tumor stromal cells. Full article
(This article belongs to the Special Issue The Role of Immunity in the Tumor Microenvironment)
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Review

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16 pages, 1194 KiB  
Review
The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions
by Taha Ahmedna, Harmon Khela, Carly Weber-Levine, Tej D. Azad, Christopher M. Jackson, Kathleen Gabrielson, Chetan Bettegowda and Jordina Rincon-Torroella
Cancers 2023, 15(24), 5784; https://doi.org/10.3390/cancers15245784 - 10 Dec 2023
Cited by 1 | Viewed by 960
Abstract
Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review [...] Read more.
Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM. Full article
(This article belongs to the Special Issue The Role of Immunity in the Tumor Microenvironment)
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24 pages, 2044 KiB  
Review
Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?
by Christina Brummer, Tobias Pukrop, Joachim Wiskemann, Christina Bruss, Ines Ugele and Kathrin Renner
Cancers 2023, 15(18), 4668; https://doi.org/10.3390/cancers15184668 - 21 Sep 2023
Cited by 2 | Viewed by 1742
Abstract
Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor [...] Read more.
Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment. Exercise is known to promote immune cell circulation and improve immunosurveillance. Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME) and therefore enhance anti-tumor immunity. This suggests a favorable impact of exercise on the efficacy of ICI. Our review delivers insight into possible molecular mechanisms of the crosstalk between muscle, tumor, and immune cells. It summarizes current data on exercise-induced effects on anti-tumor immunity and ICI in mice and men. We consider preclinical and clinical study design challenges and discuss the role of cancer type, exercise frequency, intensity, time, and type (FITT) and immune sensitivity as critical factors for exercise-induced impact on cancer immunosurveillance. Full article
(This article belongs to the Special Issue The Role of Immunity in the Tumor Microenvironment)
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