Progression of the Immune Escape Mechanism in Tumors

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cancer Biology".

Deadline for manuscript submissions: 31 March 2024 | Viewed by 21421

Special Issue Editors

Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, NY, USA
Interests: immunooncology; cancer immunotherapy; cancer signaling; translational cancer research; T cells; macrophages; NK cells
Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA
Interests: cancer biology; extracellular vesicles; radiation oncology; clinical pathology; immunoncology; dendritic cells; tumor microenvironment

Special Issue Information

Dear Colleagues,

There is a long-standing research interest to understand the molecular interactions between tumor cells and the innate and adaptative immune cells that are present in the tumor microenvironment (TME) (CD8 T cells, dendritic cells, macrophages, NK cells etc.). Onset of immunesuppression via various mechanisms in these immune cells in the TME can potentially results in cancer cells escaping that effects the antitumor immune responses. This cancer immune escape phenomenon leads to further cancer growth and greater tumor burden. Therefore, understanding these immune–inhibitory interactions and inhibiting them can potentially produce a robust anti-tumor immune response. Recently, the targeting of immunesuppresive pathways in tumors has taken precedence, and the inhibition of “immune checkpoint’ pathways” (such as CTLA4, PD1, PDL1 etc.) have revolutionized translational cancer research in patients. In this Special Issue titled “Progression of the Immune Escape Mechanism in Tumors”, we aim to curate and show case scientific studies about immune escape mechanisms in cancers, with the aim that it will lead to further progress in the research field of tumor immunology and immunotherapy. We hope this Special Issue will address the paramount need to study and decipher novel and existing immunosuppressive pathways that can have therapeutic implications in different tumor types. We anticipate that this Special Issue will also pave the path for future studies which will utilize the gained knowledge in designing effective therapeutic tools that will ultimately help in cancer management in patients.

Dr. Sumit Mukherjee
Dr. Sheila Spada
Guest Editors

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Keywords

  • cancer immunology
  • immune checkpoints
  • cancer immunotherapy
  • cancer immune escape 
  • Immuno-oncology
  • CAR T cells

Published Papers (3 papers)

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Review

15 pages, 871 KiB  
Review
Immune Escape in Glioblastoma: Mechanisms of Action and Implications for Immune Checkpoint Inhibitors and CAR T-Cell Therapy
by Catherine Yu, Kristin Hsieh, Daniel R. Cherry, Anthony D. Nehlsen, Lucas Resende Salgado, Stanislav Lazarev and Kunal K. Sindhu
Biology 2023, 12(12), 1528; https://doi.org/10.3390/biology12121528 - 15 Dec 2023
Viewed by 1495
Abstract
Glioblastoma, the most common primary brain cancer in adults, is characterized by a poor prognosis and resistance to standard treatments. The advent of immunotherapy has revolutionized the treatment of several cancers in recent years but has failed to demonstrate benefit in patients with [...] Read more.
Glioblastoma, the most common primary brain cancer in adults, is characterized by a poor prognosis and resistance to standard treatments. The advent of immunotherapy has revolutionized the treatment of several cancers in recent years but has failed to demonstrate benefit in patients with glioblastoma. Understanding the mechanisms by which glioblastoma exerts tumor-mediated immune suppression in both the tumor microenvironment and the systemic immune landscape is a critical step towards developing effective immunotherapeutic strategies. In this review, we discuss the current understanding of immune escape mechanisms in glioblastoma that compromise the efficacy of immunotherapies, with an emphasis on immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. In parallel, we review data from preclinical studies that have identified additional therapeutic targets that may enhance overall treatment efficacy in glioblastoma when administered alongside existing immunotherapies. Full article
(This article belongs to the Special Issue Progression of the Immune Escape Mechanism in Tumors)
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43 pages, 1049 KiB  
Review
Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors
by Shovan Dutta, Anirban Ganguly, Kaushiki Chatterjee, Sheila Spada and Sumit Mukherjee
Biology 2023, 12(2), 218; https://doi.org/10.3390/biology12020218 - 30 Jan 2023
Cited by 28 | Viewed by 11651
Abstract
Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination [...] Read more.
Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination strategies to improve the current ICIs. In this review, we discuss some approved immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and also highlight newer emerging ICIs. For instance, HLA-E, overexpressed by tumor cells, represents an immune-suppressive feature by binding CD94/NKG2A, on NK and T cells. NKG2A blockade recruits CD8+ T cells and activates NK cells to decrease the tumor burden. NKG2D acts as an NK cell activating receptor that can also be a potential ICI. The adenosine A2A and A2B receptors, CD47-SIRPα, TIM-3, LAG-3, TIGIT, and VISTA are targets that also contribute to cancer immunoresistance and have been considered for clinical trials. Their antitumor immunosuppressive functions can be used to develop blocking antibodies. PARPs, mARTs, and B7-H3 are also other potential targets for immunosuppression. Additionally, miRNA, mRNA, and CRISPR-Cas9-mediated immunotherapeutic approaches are being investigated with great interest. Pre-clinical and clinical studies project these targets as potential immunotherapeutic candidates in different cancer types for their robust antitumor modulation. Full article
(This article belongs to the Special Issue Progression of the Immune Escape Mechanism in Tumors)
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29 pages, 12144 KiB  
Review
Extracellular Vesicles: New Classification and Tumor Immunosuppression
by Mona Sheta, Eman A. Taha, Yanyin Lu and Takanori Eguchi
Biology 2023, 12(1), 110; https://doi.org/10.3390/biology12010110 - 10 Jan 2023
Cited by 20 | Viewed by 7339
Abstract
Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological biomarkers and delivered to recipient cells whose fates are often altered in local and distant tissues. Classical EVs are exosomes, microvesicles, and apoptotic [...] Read more.
Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles carrying various types of molecules. These EV cargoes are often used as pathophysiological biomarkers and delivered to recipient cells whose fates are often altered in local and distant tissues. Classical EVs are exosomes, microvesicles, and apoptotic bodies, while recent studies discovered autophagic EVs, stressed EVs, and matrix vesicles. Here, we classify classical and new EVs and non-EV nanoparticles. We also review EVs-mediated intercellular communication between cancer cells and various types of tumor-associated cells, such as cancer-associated fibroblasts, adipocytes, blood vessels, lymphatic vessels, and immune cells. Of note, cancer EVs play crucial roles in immunosuppression, immune evasion, and immunotherapy resistance. Thus, cancer EVs change hot tumors into cold ones. Moreover, cancer EVs affect nonimmune cells to promote cellular transformation, including epithelial-to-mesenchymal transition (EMT), chemoresistance, tumor matrix production, destruction of biological barriers, angiogenesis, lymphangiogenesis, and metastatic niche formation. Full article
(This article belongs to the Special Issue Progression of the Immune Escape Mechanism in Tumors)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Exploring the Immunological Dynamics and Evasion Strategies in Hepatocellular Carcinoma: Unveiling the prospects of Immunotherapies

Shayanki Lahiri, Ph.D.1, Kaushik Banerjee, Ph.D.2, 3*

 

1Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States.

2Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, United States.

3Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States.

*Correspondence: Kaushik Banerjee, Ph.D., Department of Neurosurgery, Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States. Email: kaushb@umich.edu; kaushb@med.umich.edu.

 

Abstract:

Hepatocellular carcinoma (HCC) accounts for ~90% of primary liver cancers and third leading cause of tumor-related mortality worldwide. World Health Organization estimates that more than one million people will die from HCC in 2030. Despite great breakthrough in immune or combination therapy, majority of HCC patients fail to respond to these treatments due to drug resistance through immune evasion or frequent recurrence through modulating tumor microenvironment (TME). Liver is the central immunomodulator that ensures organ and systemic protection while maintaining immune tolerance. Deregulation of the immunological axis in liver and hepatitis B or C virus infection causes chronic inflammation that leads to the development of HCC. Deregulated extracellular matrix, abnormal angiogenesis and chronic inflammation collectively contributes to the immunosuppressive TME that helps in the development of HCC. Immunosuppressive TME interacts with various immune populations to help tumor cell migration and survival. Along with TME, other immunosuppressive cells, co-inhibitory signals, soluble cytokines, metabolically hostile TME, gut microbiota and different immune signaling cascades can largely contribute to the immune modulation and immune evasion mechanisms of HCC. Currently, very little is known about the immunotherapy treatment failure and predictors of response to these therapeutic strategies to facilitate the patient stratification. Knowledge about how HCC tumor immune microenvironment (TIME) affects HCC targeting will help to prevent immune evasion and development of therapeutic resistance against HCC. With the recent success of immune and combination therapies, there is an urgent need to understand the mechanisms of immune evasion and resistance to immune or alternative therapies in HCC. Here we summarize the current knowledge about different immune escape strategies of HCC underlying the role of TIME, discuss the dynamic interactions of TIME and propose therapeutic strategies for more effective immunotherapy.

 

2. Title: “Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion”

Authors: Ankita Mitra1, Anoop Kumar2, Nitin Amdare3, Rajiv Pathak4,#

Affiliation:

 1Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, United States

2Molecular Diagnostic Laboratory, National Institute of Biologicals, Noida, U.P. India

3Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA

4Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA

 #Corresponding author: Rajiv Pathak (Email: rajivpathak17@gmail.com)

 Type of article: Review article

 Abstract

Cancer immune evasion represents a leading hallmark of cancer, posing a significant obstacle to the development of successful anticancer therapies. However, the landscape of cancer treatment has significantly evolved, transitioning into the era of immunotherapy from conventional methods such as surgical resection, radiotherapy, chemotherapy, and targeted drug therapy. Immunotherapy has emerged as a pivotal component in cancer treatment, harnessing the body's immune system to combat cancer and offering improved prognostic outcomes for numerous patients. The remarkable success of immunotherapy has spurred significant efforts to enhance the clinical efficacy of existing agents and strategies. Several immunotherapeutic approaches have received approval for targeted cancer treatments, while others are currently in preclinical and clinical trials. This review explores recent progress in unraveling the mechanisms of cancer immune evasion and evaluates the clinical effectiveness of diverse immunotherapy strategies, including cancer vaccines, adoptive cell therapy, and antibody-based treatments. It encompasses both established treatments and those currently under investigation, providing a comprehensive overview of efforts to combat cancer through immunological approaches. Additionally, the article emphasizes the current developments, limitations, and challenges in cancer immunotherapy. Furthermore, by integrating analyses of cancer immunotherapy resistance mechanisms, exploring combination strategies, and personalized approaches, it offers valuable insights crucial for the development of novel anticancer immunotherapeutic strategies.

 

 

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