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Vaccines
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Tumor Immunotherapy
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Tumor Immunotherapy

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 20749

Special Issue Editor

Dr. Antonino Bruno

E-Mail Website
Guest Editor
1. Laboratory of Immunology and General Pathology, University of Insubria, Varese, Italy
2. Laboratory of Innate Immunity, IRCCS MultiMedica, Milan, Italy
Interests: natural killer cells; innate lymphoid cells; tumor microenvironment; tumor angiogenesis; tumor immunology; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunotherapy has emerged as the next-generation frontier in cancer treatments, leading to relevant success in diverse cancer types, such as melanoma and lung cancer. Therefore, in this successful scenario, there is still an “unsuccessful” window for some cancer types. Immunotherapy targets, employs, and re-educates the immune cells of the host, clearly placing the tumor immune microenvironment (TIME) as a relevant orchestrator for therapeutic outcomes in cancer patients. For the “unsuccessful” window, an increasingly deep investigation on the tumor–immune cell interactions within the tumor microenvironment (TME) still represent an unmet pre-clinical and clinical need, to better design successful and TME/TIME patient-oriented (immuno)therapeutic approaches.

Potential topics for this Issue include, but are not limited to, the following:

  • The tumor (immune)-microenvironment as a target for immunotherapy;
  • Immune cell polarization and immunotherapy;
  • Immune cell angiogenic switch and immunotherapy;
  • Molecular pathways in immunotherapy;
  • Strategies to re-educate immune cells in cancers;
  • Combination therapies acting on the immune system in cancer;
  • Delivering strategies in immunotherapy;
  • Nanotechnologies in immunotherapy;
  • Phytochemicals endowed with immunostimulatory actions for immunotherapy approaches, including vaccines;
  • Marine drugs endowed with immunostimulatory actions for immunotherapy approaches, including vaccines.

Dr. Antonino Bruno
Guest Editor

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.

Keywords

  • innate immunity
  • adaptive immunity
  • immune cell polarization
  • immune cell re-education
  • immunotherapy
  • combinations in/with immunotherapy

Published Papers (6 papers)

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Research

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15 pages, 1816 KiB  
Article
Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival
by Salman M. Toor, Varun Sasidharan Nair, Reem Saleh, Rowaida Z. Taha, Khaled Murshed, Mahmood Al-Dhaheri, Mahwish Khawar, Ayman A. Ahmed, Mohamed A. Kurer, Mohamed Abu Nada and Eyad Elkord
Vaccines 2021, 9(4), 334; https://doi.org/10.3390/vaccines9040334 - 01 Apr 2021
Cited by 5 | Viewed by 2265
Abstract
Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed [...] Read more.
Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients. Full article
(This article belongs to the Special Issue Tumor Immunotherapy)
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17 pages, 3437 KiB  
Article
Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy
by Marco Carlo Merlano, Andrea Abbona, Matteo Paccagnella, Antonella Falletta, Cristina Granetto, Vincenzo Ricci, Elena Fea, Nerina Denaro, Fiorella Ruatta, Anna Merlotti, Oscar Bertetto, Nicola Crosetto, Danilo Galizia, Marco Basiricò, Loretta Gammaitoni, Dario Sangiolo, Massimo Aglietta and Ornella Garrone
Vaccines 2021, 9(3), 235; https://doi.org/10.3390/vaccines9030235 - 08 Mar 2021
Cited by 3 | Viewed by 2748
Abstract
Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment [...] Read more.
Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients’ outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39). Full article
(This article belongs to the Special Issue Tumor Immunotherapy)
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14 pages, 2569 KiB  
Article
Tumor-Infiltrating Lymphoid Cells in Colorectal Cancer Patients with Varying Disease Stages and Microsatellite Instability-High/Stable Tumors
by Salman M. Toor, Varun Sasidharan Nair, Khaled Murshed, Mohamed Abu Nada and Eyad Elkord
Vaccines 2021, 9(1), 64; https://doi.org/10.3390/vaccines9010064 - 19 Jan 2021
Cited by 14 | Viewed by 3683
Abstract
Immune checkpoint inhibition is an effective anti-cancer therapeutic approach but has shown limited efficacy in treating colorectal cancer (CRC) patients. Importantly, immune constituents of the tumor microenvironment (TME) can influence therapy response and cancer progression. We investigated the expression of immune checkpoints (ICs) [...] Read more.
Immune checkpoint inhibition is an effective anti-cancer therapeutic approach but has shown limited efficacy in treating colorectal cancer (CRC) patients. Importantly, immune constituents of the tumor microenvironment (TME) can influence therapy response and cancer progression. We investigated the expression of immune checkpoints (ICs) on lymphoid populations within the CRC TME and compared with cells from normal colon tissues using samples from 50 patients with varying disease stages. We found that the levels of B cells, T cells, and NK cells were similar, IC-expressing CD4+ and CD4+CD8+ double positive T cells were higher, while CD8+ T cells and CD4−CD8− double negative T cells were significantly lower in CRC tumors. Notably, patients with mismatch-repair deficiency/microsatellite instability-high tumors had higher levels of IC-expressing CD4+ and CD8+ T cells than patients with proficient MMR and microsatellite stable tumors. Lastly, The Cancer Genome Atlas Colon Adenocarcinoma datasets showed associations between low expression of selective genes and poorer progression-free interval. Our findings highlight differential expression of ICs on lymphoid cells in CRC tumors in the era of cancer immunotherapy, which at present is solely approved for anti-PD-1 therapy in patients with dMMR/MSI-H tumors. Further investigations into their functionality have potentials for deciphering resistance mechanisms to IC inhibition. Full article
(This article belongs to the Special Issue Tumor Immunotherapy)
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Review

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13 pages, 2021 KiB  
Review
Neutrophil and Natural Killer Cell Interactions in Cancers: Dangerous Liaisons Instructing Immunosuppression and Angiogenesis
by Maria Teresa Palano, Matteo Gallazzi, Martina Cucchiara, Andrea De Lerma Barbaro, Daniela Gallo, Barbara Bassani, Antonino Bruno and Lorenzo Mortara
Vaccines 2021, 9(12), 1488; https://doi.org/10.3390/vaccines9121488 - 16 Dec 2021
Cited by 8 | Viewed by 3642
Abstract
The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset and progression, as a consequence of the phenotype/functional plasticity and adaptation capabilities of tumor-infiltrating and tumor-associated immune cells. Immune cells within the tumor micro (tissue-local) and macro (peripheral blood) [...] Read more.
The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset and progression, as a consequence of the phenotype/functional plasticity and adaptation capabilities of tumor-infiltrating and tumor-associated immune cells. Immune cells within the tumor micro (tissue-local) and macro (peripheral blood) environment closely interact by cell-to-cell contact and/or via soluble factors, also generating a tumor-permissive soil. These dangerous liaisons have been investigated for pillars of tumor immunology, such as tumor associated macrophages and T cell subsets. Here, we reviewed and discussed the contribution of selected innate immunity effector cells, namely neutrophils and natural killer cells, as “soloists” or by their “dangerous liaisons”, in favoring tumor progression by dissecting the cellular and molecular mechanisms involved. Full article
(This article belongs to the Special Issue Tumor Immunotherapy)
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21 pages, 1834 KiB  
Review
Metabolic Rewiring in the Tumor Microenvironment to Support Immunotherapy: A Focus on Neutrophils, Polymorphonuclear Myeloid-Derived Suppressor Cells and Natural Killer Cells
by Andrea De Lerma Barbaro, Maria Teresa Palano, Martina Cucchiara, Matteo Gallazzi, Lorenzo Mortara and Antonino Bruno
Vaccines 2021, 9(10), 1178; https://doi.org/10.3390/vaccines9101178 - 14 Oct 2021
Cited by 5 | Viewed by 2731
Abstract
Leukocytes often undergo rapid changes in cell phenotype, for example, from a resting to an activated state, which places significant metabolic demands on the cell. These rapid changes in metabolic demand need to be tightly regulated to support immune cell effector functions during [...] Read more.
Leukocytes often undergo rapid changes in cell phenotype, for example, from a resting to an activated state, which places significant metabolic demands on the cell. These rapid changes in metabolic demand need to be tightly regulated to support immune cell effector functions during the initiation and downregulation of an immune response. Prospects for implementing cancer immunotherapy also rest on the idea of optimizing the metabolic profile of immune cell effectors. Here, we examine this issue by focusing on neutrophils and NK cells as cells of increasing interest in cancer immunology and tumor immunometabolism, because they can be targeted or, in the case of NK, used as effectors in immunotherapy. In addition, neutrophils and NK cells have been shown to functionally interact. In the case of neutrophils, we also extended our interest to polymorphonuclear MDSC (PMN-MDSCs), since the granulocytic subset of MDSCs share many phenotypes and are functionally similar to pro-tumor neutrophils. Finally, we reviewed relevant strategies to target tumor metabolism, focusing on neutrophils and NK cells. Full article
(This article belongs to the Special Issue Tumor Immunotherapy)
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15 pages, 352 KiB  
Review
Bacillus Calmette–Guérin Immunotherapy for Cancer
by Fabíola Cardillo, Maiara Bonfim, Periela da Silva Vasconcelos Sousa, José Mengel, Luiz Roberto Ribeiro Castello-Branco and Rosa Teixeira Pinho
Vaccines 2021, 9(5), 439; https://doi.org/10.3390/vaccines9050439 - 01 May 2021
Cited by 25 | Viewed by 4643
Abstract
Bacillus Calmette–Guérin (BCG), an attenuated vaccine from Mycobacterium bovis, was initially developed as an agent for vaccination against tuberculosis. BCG proved to be the first successful immunotherapy against established human bladder cancer and other neoplasms. The use of BCG has been shown [...] Read more.
Bacillus Calmette–Guérin (BCG), an attenuated vaccine from Mycobacterium bovis, was initially developed as an agent for vaccination against tuberculosis. BCG proved to be the first successful immunotherapy against established human bladder cancer and other neoplasms. The use of BCG has been shown to induce a long-lasting antitumor response over all other forms of treatment against intermediate, non-invasive muscle bladder cancer Several types of tumors may now be treated by releasing the immune response through the blockade of checkpoint inhibitory molecules, such as CTLA-4 and PD-1. In addition, Toll-Like Receptor (TLR) agonists and BCG are used to potentiate the immune response against tumors. Studies concerning TLR-ligands combined with BCG to treat melanoma have demonstrated efficacy in treating mice and patients This review addresses several interventions using BCG on neoplasms, such as Leukemia, Bladder Cancer, Lung Cancer, and Melanoma, describing treatments and antitumor responses promoted by this attenuated bacillus. Of essential importance, BCG is described recently to participate in an adequate microbiome, establishing an effective response during cell-target therapy when combined with anti-PD-1 antibody, which stimulates T cell responses against the melanoma. Finally, trained immunity is discussed, and reprogramming events to shape innate immune responses are addressed. Full article
(This article belongs to the Special Issue Tumor Immunotherapy)
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