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Vaccines
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Cancer Immunology Focus: Cellular & Molecular Immunology
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Cancer Immunology Focus: Cellular & Molecular Immunology

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cellular/Molecular Immunology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 30666

Special Issue Editors

Dr. Pasupathi Sundaramoorthy

E-Mail Website
Guest Editor
Carolina BioOncology Institute, Huntersville, NC 28078, USA
Interests: cancer therapy
Dr. D. S. Prabakaran

E-Mail Website
Guest Editor
Department of Radiation Oncology, College of Medicine, Chungbuk National University, Chungdae-ro 1, Seowon-gu, Cheongju 28644, Republic of Korea
Interests: radiation resistance (X-ray, C-ion); EGFR signaling; notch signaling; epithelial mesenchymal transition (EMT); cancer stem cells (CSCs); cancer immunotherapy; radiation protection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A cure for cancer remains elusive. Conventional cancer treatment, such as chemotherapy, radiotherapy, and targeted therapy, are showed improvements for cancer patients. However, patients eventually relapse and develop resistance to conventional treatments. Immunotherapy of cancer is a rapidly evolving field and showed significant improvements for cancer patients in terms of survival and quality of life for multiple cancer including hematological and solid malignancies. Several types of immune therapy ongoing including, activating immune system against cancer cell through checkpoints inhibitor, CAR-T, monoclonal antibody, vaccine, ati-cancer drug and suppressing immune cell inhibitor such as MDSC and Treg. In this special issue, we plan to focus invitro and invivo studies of cellular and molecular mechanisms of immunotherapy for cancer treatment. Furthermore, we will discuss the pre- clinical, clinical, and experimental evidence to uncover the mechanisms related to immunotherapy and combination therapeutic approaches. We warmly welcome all scientists working in these fields are cordially invited to submit their manuscripts to our special issue.

We look forward to receiving your contributions.

Dr. Pasupathi Sundaramoorthy
Dr. D. S. Prabakaran
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. Vaccines is an international peer-reviewed open access monthly 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 2700 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.

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Published Papers (9 papers)

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Research

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15 pages, 2876 KiB  
Article
Immune Profile of Blood, Tissue and Peritoneal Fluid: A Comparative Study in High Grade Serous Epithelial Ovarian Cancer Patients at Interval Debulking Surgery
by Pavan Kumar, Samruddhi Ranmale, Hemant Tongaonkar and Jayanti Mania-Pramanik
Vaccines 2022, 10(12), 2121; https://doi.org/10.3390/vaccines10122121 - 12 Dec 2022
Cited by 3 | Viewed by 2332
Abstract
High-grade serous epithelial ovarian carcinoma (HGSOC) is an immunogenic tumor with a unique tumor microenvironment (TME) that extends to the peritoneal cavity. The immunosuppressive nature of TME imposes the major challenge to develop effective treatment options for HGSOC. Interaction of immune cells in [...] Read more.
High-grade serous epithelial ovarian carcinoma (HGSOC) is an immunogenic tumor with a unique tumor microenvironment (TME) that extends to the peritoneal cavity. The immunosuppressive nature of TME imposes the major challenge to develop effective treatment options for HGSOC. Interaction of immune cells in TME is an important factor. Hence, a better understanding of immune profile of TME may be required for exploring alternative treatment options. Immune profiling of peritoneal fluid (PF), tumor specimens, and blood were carried out using flowcytometry, ELISA, and Procartaplex immunoassay. The frequency of CD56BrightNK cells and expression of functional receptors were reduced in PF. Increased activating NKp46+CD56DimNK cells may indicate differential antitumor response in PF. Functional receptors on NK, NKT-like and T cells were reduced more drastically in tumor specimens. Soluble ligands MIC-B and PVR were reduced, whereas B7-H6 was increased in PF. Dissemination of tumor cells contributes to soluble ligands in PF. A differential cytokine profile was found in serum and PF as IL-2, IL-8, IL-15, IL-27, IFN-γ, and GM-CSF were elevated specifically in PF. In conclusion, the differential immune profile and correlation of soluble parameters and NK cell receptors with chemo response score may add knowledge to understand anti-tumor immune response to develop effective treatment modality. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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11 pages, 2167 KiB  
Article
Correlations between Circulating and Tumor-Infiltrating CD4+ Treg Subsets with Immune Checkpoints in Colorectal Cancer Patients with Early and Advanced Stages
by Mohammad A. Al-Mterin, Khaled Murshed and Eyad Elkord
Vaccines 2022, 10(9), 1471; https://doi.org/10.3390/vaccines10091471 - 5 Sep 2022
Cited by 8 | Viewed by 2431
Abstract
The existence of various T regulatory cell (Treg) subsets in colorectal cancer (CRC) could play a variety of functions in the regulation of anti-cancer immunity. We studied correlations between CD4+ Treg subsets with the expression of immunological checkpoints on CD4+ T [...] Read more.
The existence of various T regulatory cell (Treg) subsets in colorectal cancer (CRC) could play a variety of functions in the regulation of anti-cancer immunity. We studied correlations between CD4+ Treg subsets with the expression of immunological checkpoints on CD4+ T cells, including PD-1, TIM-3, LAG-3, and CTLA-4 in CRC patients with early and advanced TNM staging. Strong positive correlations were found between frequencies of FoxP3+ Tregs and FoxP3+Helios+ Tregs with frequencies of various immune checkpoint-expressing CD4+ T cells in the tumor microenvironment (TME). However, there were strong negative correlations between frequencies of FoxP3−Helios− T cells and these immune checkpoint-expressing CD4+ T cells. Specifically, in the TME, we found that the correlations between FoxP3+ Tregs, FoxP3+Helios+ Tregs, FoxP3+Helios− Tregs, and FoxP3−Helios− T cells with CD4+LAG-3+ T cells and CD4+CTLA-4+ T cells were higher in patients with early stages, suggesting the potential of these highly immunosuppressive cells in inhibiting inflammatory responses in the TME. However, the correlations between FoxP3+ Tregs, FoxP3+Helios+ Tregs, and FoxP3−Helios− T cells with CD4+TIM-3+ T cells were higher in patients with advanced stages. This is the first study to explore correlations of Treg subpopulations with immune checkpoint-expressing CD4+ T cells in CRC based on clinicopathological features of CRC patients. The findings of our study provide a justification for focusing on these cells that possess highly immunosuppressive features. Understanding the correlations between different immune checkpoints and Treg subsets in CRC patients has the potential to enhance our understanding of core mechanisms of Treg-mediated immunosuppression in cancer. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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Review

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36 pages, 1709 KiB  
Review
Advances in the Lung Cancer Immunotherapy Approaches
by Hafiza Padinharayil, Reema Rose Alappat, Liji Maria Joy, Kavya V. Anilkumar, Cornelia M. Wilson, Alex George, Abilash Valsala Gopalakrishnan, Harishkumar Madhyastha, Thiyagarajan Ramesh, Ezhaveni Sathiyamoorthi, Jintae Lee and Raja Ganesan
Vaccines 2022, 10(11), 1963; https://doi.org/10.3390/vaccines10111963 - 19 Nov 2022
Cited by 8 | Viewed by 3120
Abstract
Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of [...] Read more.
Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains. Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised. Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions. We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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20 pages, 1269 KiB  
Review
Immunomodulatory Role of Thioredoxin Interacting Protein in Cancer’s Impediments: Current Understanding and Therapeutic Implications
by Ramkumar Katturajan, Sangeetha Nithiyanandam, Manisha Parthasarathy, Abilash Valsala Gopalakrishnan, Ezhaveni Sathiyamoorthi, Jintae Lee, Thiyagarajan Ramesh, Mahalaxmi Iyer, Sabina Evan Prince and Raja Ganesan
Vaccines 2022, 10(11), 1902; https://doi.org/10.3390/vaccines10111902 - 10 Nov 2022
Cited by 6 | Viewed by 2895
Abstract
Cancer, which killed ten million people in 2020, is expected to become the world’s leading health problem and financial burden. Despite the development of effective therapeutic approaches, cancer-related deaths have increased by 25.4% in the last ten years. Current therapies promote apoptosis and [...] Read more.
Cancer, which killed ten million people in 2020, is expected to become the world’s leading health problem and financial burden. Despite the development of effective therapeutic approaches, cancer-related deaths have increased by 25.4% in the last ten years. Current therapies promote apoptosis and oxidative stress DNA damage and inhibit inflammatory mediators and angiogenesis from providing temporary relief. Thioredoxin-binding protein (TXNIP) causes oxidative stress by inhibiting the function of the thioredoxin system. It is an important regulator of many redox-related signal transduction pathways in cells. In cancer cells, it functions as a tumor suppressor protein that inhibits cell proliferation. In addition, TXNIP levels in hemocytes increased after immune stimulation, suggesting that TXNIP plays an important role in immunity. Several studies have provided experimental evidence for the immune modulatory role of TXNIP in cancer impediments. TXNIP also has the potential to act against immune cells in cancer by mediating the JAK-STAT, MAPK, and PI3K/Akt pathways. To date, therapies targeting TXNIP in cancer are still under investigation. This review highlights the role of TXNIP in preventing cancer, as well as recent reports describing its functions in various immune cells, signaling pathways, and promoting action against cancer. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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21 pages, 1126 KiB  
Review
Role of Immune Cells and Receptors in Cancer Treatment: An Immunotherapeutic Approach
by Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, Arunraj Namachivayam, Reshma Murali, D. S. Prabakaran, Raja Ganesan, Kaviyarasi Renu, Abhijit Dey, Balachandar Vellingiri, Gnanasambandan Ramanathan, George Priya Doss C. and Abilash Valsala Gopalakrishnan
Vaccines 2022, 10(9), 1493; https://doi.org/10.3390/vaccines10091493 - 7 Sep 2022
Cited by 15 | Viewed by 3509
Abstract
Cancer immunotherapy moderates the immune system’s ability to fight cancer. Due to its extreme complexity, scientists are working to put together all the puzzle pieces to get a clearer picture of the immune system. Shreds of available evidence show the connection between cancer [...] Read more.
Cancer immunotherapy moderates the immune system’s ability to fight cancer. Due to its extreme complexity, scientists are working to put together all the puzzle pieces to get a clearer picture of the immune system. Shreds of available evidence show the connection between cancer and the immune system. Immune responses to tumors and lymphoid malignancies are influenced by B cells, γδT cells, NK cells, and dendritic cells (DCs). Cancer immunotherapy, which encompasses adoptive cancer therapy, monoclonal antibodies (mAbs), immune checkpoint therapy, and CART cells, has revolutionized contemporary cancer treatment. This article reviews recent developments in immune cell regulation and cancer immunotherapy. Various options are available to treat many diseases, particularly cancer, due to the progress in various immunotherapies, such as monoclonal antibodies, recombinant proteins, vaccinations (both preventative and curative), cellular immunotherapies, and cytokines. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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15 pages, 597 KiB  
Review
Molecular Crosstalk between the Immunological Mechanism of the Tumor Microenvironment and Epithelial–Mesenchymal Transition in Oral Cancer
by Kaviyarasi Renu, Sathishkumar Vinayagam, Vishnu Priya Veeraraghavan, Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, D. S. Prabakaran, Raja Ganesan, Abhijit Dey, Balachandar Vellingiri, Sabariswaran Kandasamy, Gnanasambandan Ramanathan, George Priya Doss C, Alex George and Abilash Valsala Gopalakrishnan
Vaccines 2022, 10(9), 1490; https://doi.org/10.3390/vaccines10091490 - 7 Sep 2022
Viewed by 2279
Abstract
Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one [...] Read more.
Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one of the most exigent tumors to control and treat. The survival rate of oral cancer is poor due to local invasion along with recurrent lymph node metastasis. The tumor microenvironment contains a different population of cells, such as fibroblasts associated with cancer, immune-infiltrating cells, and other extracellular matrix non-components. Metastasis in a primary site is mainly due to multifaceted progression known as epithelial-to-mesenchymal transition (EMT). For the period of EMT, epithelial cells acquire mesenchymal cell functional and structural characteristics, which lead to cell migration enhancement and promotion of the dissemination of tumor cells. The present review links the tumor microenvironment and the role of EMT in inflammation, transcriptional factors, receptor involvement, microRNA, and other signaling events. It would, in turn, help to better understand the mechanism behind the tumor microenvironment and EMT during oral cancer. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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16 pages, 1341 KiB  
Review
The Cellular and Molecular Immunotherapy in Prostate Cancer
by Anirban Goutam Mukherjee, Uddesh Ramesh Wanjari, D. S. Prabakaran, Raja Ganesan, Kaviyarasi Renu, Abhijit Dey, Balachandar Vellingiri, Sabariswaran Kandasamy, Thiyagarajan Ramesh and Abilash Valsala Gopalakrishnan
Vaccines 2022, 10(8), 1370; https://doi.org/10.3390/vaccines10081370 - 22 Aug 2022
Cited by 15 | Viewed by 3662
Abstract
In recent history, immunotherapy has become a viable cancer therapeutic option. However, over many years, its tenets have changed, and it now comprises a range of cancer-focused immunotherapies. Clinical trials are currently looking into monotherapies or combinations of medicines that include immune checkpoint [...] Read more.
In recent history, immunotherapy has become a viable cancer therapeutic option. However, over many years, its tenets have changed, and it now comprises a range of cancer-focused immunotherapies. Clinical trials are currently looking into monotherapies or combinations of medicines that include immune checkpoint inhibitors (ICI), CART cells, DNA vaccines targeting viruses, and adoptive cellular therapy. According to ongoing studies, the discipline should progress by incorporating patient-tailored immunotherapy, immune checkpoint blockers, other immunotherapeutic medications, hormone therapy, radiotherapy, and chemotherapy. Despite significantly increasing morbidity, immunotherapy can intensify the therapeutic effect and enhance immune responses. The findings for the immunotherapy treatment of advanced prostate cancer (PCa) are compiled in this study, showing that is possible to investigate the current state of immunotherapy, covering new findings, PCa treatment techniques, and research perspectives in the field’s unceasing evolution. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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15 pages, 1200 KiB  
Review
EGFR-Based Targeted Therapy for Colorectal Cancer—Promises and Challenges
by Balakarthikeyan Janani, Mayakrishnan Vijayakumar, Kannappan Priya, Jin Hee Kim, D. S. Prabakaran, Mohammad Shahid, Sameer Al-Ghamdi, Mohammed Alsaidan, Nasraddin Othman Bahakim, Mohammad Hassan Abdelzaher and Thiyagarajan Ramesh
Vaccines 2022, 10(4), 499; https://doi.org/10.3390/vaccines10040499 - 24 Mar 2022
Cited by 38 | Viewed by 4850
Abstract
Colorectal carcinoma (CRC) is the most lethal and common form of cancer in the world. It was responsible for almost 881,000 cancer deaths in 2018. Approximately 25% of cases are diagnosed at advanced stages with metastasis—this poses challenges for effective surgical control and [...] Read more.
Colorectal carcinoma (CRC) is the most lethal and common form of cancer in the world. It was responsible for almost 881,000 cancer deaths in 2018. Approximately 25% of cases are diagnosed at advanced stages with metastasis—this poses challenges for effective surgical control and future tumor-related mortality. There are numerous diagnostic methods that can be used to reduce the risk of colorectal carcinoma. Among these, targeted nanotherapy aims to eliminate the tumor and any metastasis. Active targeting can increase the effectiveness and quantity of drugs delivered to the target site. Antibodies that target overexpressed receptors on cell surfaces and indicators are coupled with drug-loaded carriers. The major target receptors of chemotherapeutic drugs delivery include VEGFR, EGFR, FGFR, HER2, and TGF. On account of its major and diverse roles in cancer, it is important to target EGFR in particular for better tumor selection, as EGFR is overexpressed in 25 to 82% of colorectal carcinoma cases. The EGFR monoclonal immunoglobulins cetuximab/panitumumab can thus be used to treat colorectal cancer. This review examines carriers that contain cetuximab-conjugated therapeutic drugs as well as their efficacy in anticancer activities. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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17 pages, 2382 KiB  
Review
Probiotics in Counteracting the Role of Neutrophils in Cancer Metastasis
by Upasana Mangrolia and Jabez W. Osborne
Vaccines 2021, 9(11), 1306; https://doi.org/10.3390/vaccines9111306 - 10 Nov 2021
Cited by 7 | Viewed by 3326
Abstract
Neutrophils are known for their role geared towards pathogen clearance by different mechanisms that they initiate, primarily by the release of neutrophil extracellular traps (NETs). However, their immune-surveillance capacity accompanied with plasticity in existing as interchangeable subsets, discovered recently, has revealed their property [...] Read more.
Neutrophils are known for their role geared towards pathogen clearance by different mechanisms that they initiate, primarily by the release of neutrophil extracellular traps (NETs). However, their immune-surveillance capacity accompanied with plasticity in existing as interchangeable subsets, discovered recently, has revealed their property to contribute to complex cancer pathologies including tumor initiation, growth, angiogenesis and metastasis. Although there is a growing body of evidence suggesting a critical balance between the protumoral and antitumoral neutrophil phenotypes, an in-depth signaling pathway analysis would aid in determination of anticipatory, diagnostic and therapeutic targets. This review presents a comprehensive overview of the potential pathways involved in neutrophil-triggered cancer metastasis and introduces the influence of the microbial load and avenues for probiotic intervention. Full article
(This article belongs to the Special Issue Cancer Immunology Focus: Cellular & Molecular Immunology)
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