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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 15622

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Special Issue Editor

Dr. George Sharonov

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Guest Editor

Department of Molecular Technologies, Institute of Translational Medicine, Pirogov Russian National Research Medical University, 1 Ostrovityanova, 117997 Moscow, Russia
Interests: adaptive immunity; tumor biology; immune checkpoint; T cell receptor; tumor antigens; immune tolerance; lymphoid tissue; histology

Special Issue Information

Dear Colleagues,

Tumor development can now be tracked from its early stages owing to recent advances in genetic and instrumental techniques. Such evolutionary perspectives have made it obvious that the immune system plays a pivotal role in this process. On one hand, it imposes strong evolutionary pressure on a tumor, and cancer progression is usually associated with its loosening. The fundamental pathways of immune tolerance and exhaustion in cancer were discovered in the 1990s and revolutionized cancer treatment in the 2010s through the invention of checkpoint therapy. Several other effective approaches to boosting and targeting the immune system toward cancer cells are now undergoing clinical studies and are the matter of active research. These include adoptive cell therapies, CAR-T and TCR cloning, and vaccination with tumor-specific antigens and antibodies. On the other hand, chronic inflammation and exaggerated immune responses toward self-antigens can promote cancer due to premature immune exhaustion or accelerated mutagenesis within permanent oxidative stress. Thus, a delicate balance between inflammation and tolerance is required for effective tumor prevention or surveillance. Many of these topics have only just recently emerged in cancer research and need a better understanding to be used in practice.

In this Special Issue, we invite researchers to submit original research articles, reviews, and perspectives covering fundamental and practical aspects of tumor-immune interactions. I believe that this issue will be a valuable brick in the foundation for better cancer therapies.

Dr. George Sharonov
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 immunity
tumor evolution
tumor antigens
immune surveillance
cancer immunoediting
tumor microenvironment
immunotherapies
immune checkpoints
tumor-specific lymphocytes

Published Papers (7 papers)

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Research

Jump to: Review

22 pages, 1726 KiB

Open AccessArticle

DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved

by Natalya Risinskaya, Maria Gladysheva, Abdulpatakh Abdulpatakhov, Yulia Chabaeva, Valeriya Surimova, Olga Aleshina, Anna Yushkova, Olga Dubova, Nikolay Kapranov, Irina Galtseva, Sergey Kulikov, Tatiana Obukhova, Andrey Sudarikov and Elena Parovichnikova

Int. J. Mol. Sci. 2023, 24(24), 17602; https://doi.org/10.3390/ijms242417602 - 18 Dec 2023

Viewed by 1938

Abstract

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities—104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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16 pages, 3577 KiB

Open AccessArticle

Significance of Th17 and Treg in Treatment Efficacy and Outcome in Pediatric Acute Lymphoblastic Leukemia

by Anna Krętowska-Grunwald, Małgorzata Sawicka-Żukowska, Małgorzata Kowalska, Aleksandra Basaj, Maryna Krawczuk-Rybak, Marcin Moniuszko and Kamil Grubczak

Int. J. Mol. Sci. 2023, 24(15), 12323; https://doi.org/10.3390/ijms241512323 - 1 Aug 2023

Cited by 2 | Viewed by 1142

Abstract

Acute lymphoblastic leukemia represents a malignant proliferation of lymphoid cells blocked at an early stage of cell differentiation. It is the most common cancer occurring in children. Despite favorable prognosis, the survival rate of patients with poor treatment response or relapse remains dismal. The interaction between leukemic cells and the tumor immune microenvironment is pivotal in mediating tumor progression. In this study we evaluated associations between Treg and Th17 lymphocytes and the clinical presentation of ALL pediatric patients to validate their value in monitoring treatment outcome. The peripheral blood and bone marrow aspirates from 35 pediatric patients with ALL and 48 healthy control subjects were selected for the experiment. We demonstrated the numbers of Th17 lymphocytes and Tregs were increased in the bone marrow of ALL patients at the moment of diagnosis compared to the healthy control group, with the latter significantly decreasing during the course of ALL treatment. Patients with lower Th17 were found to demonstrate higher risk of blasts prevalence in bone marrow at day 33. ALL patients with lower WBC demonstrated higher frequency of Tregs. In summary, we identified a significant role of Th17 and Treg lymphocytes in ALL of pediatric patients and their contribution to disease-related parameters. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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18 pages, 3570 KiB

Open AccessArticle

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

by Teresa Freire, Mercedes Landeira, Cecilia Giacomini, María Florencia Festari, Álvaro Pittini, Viviana Cardozo, Alina Brosque, Leticia Monin, Valeria da Costa, Paula Faral-Tello, Carlos Robello and Eduardo Osinaga

Int. J. Mol. Sci. 2022, 23(23), 15032; https://doi.org/10.3390/ijms232315032 - 30 Nov 2022

Cited by 2 | Viewed by 1489

Abstract

Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-γ (IFN-γ) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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16 pages, 3873 KiB

Open AccessArticle

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma

by Katia Grillone, Caterina Riillo, Roberta Rocca, Serena Ascrizzi, Virginia Spanò, Francesca Scionti, Nicoletta Polerà, Annalisa Maruca, Marilia Barreca, Giada Juli, Mariamena Arbitrio, Maria Teresa Di Martino, Daniele Caracciolo, Pierosandro Tagliaferri, Stefano Alcaro, Alessandra Montalbano, Paola Barraja and Pierfrancesco Tassone

Int. J. Mol. Sci. 2022, 23(18), 10222; https://doi.org/10.3390/ijms231810222 - 6 Sep 2022

Cited by 22 | Viewed by 2296

Abstract

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA. Several findings highlighted the ability of some chemotherapeutics to induce immunogenic cell death (ICD), which is defined by the cell surface translocation of Calreticulin (CALR) via dissociation of the PP1/GADD34 complex. In this regard, we computationally predicted the ability of SIX2G to induce CALR exposure by interacting with the PP1 RVxF domain. We then assessed both the potential cytotoxic and immunogenic activity of SIX2G on in vitro models of multiple myeloma (MM), which is an incurable hematological malignancy characterized by an immunosuppressive milieu. We found that the treatment with SIX2G inhibited cell viability by inducing G2/M phase cell cycle arrest and apoptosis. Moreover, we observed the increase of hallmarks of ICD such as CALR exposure, ATP release and phospho-eIF2α protein level. Through co-culture experiments with immune cells, we demonstrated the increase of (i) CD86 maturation marker on dendritic cells, (ii) CD69 activation marker on cytotoxic T cells, and (iii) phagocytosis of tumor cells following treatment with SIX2G, confirming the onset of an immunogenic cascade. In conclusion, our findings provide a framework for further development of SIX2G as a new potential anti-MM agent. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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17 pages, 4720 KiB

Open AccessArticle

The Pyroptosis-Related Gene Prognostic Index Associated with Tumor Immune Infiltration for Pancreatic Cancer

by Wen Xie, Xiaoyi Li, Chunxiu Yang, Jiahao Li, Guoyan Shen, Hongshan Chen, Shu-Yuan Xiao and Yueying Li

Int. J. Mol. Sci. 2022, 23(11), 6178; https://doi.org/10.3390/ijms23116178 - 31 May 2022

Cited by 4 | Viewed by 2904

Abstract

Pancreatic cancer (PC) is one of the most fatal malignancies. Pyroptosis, a type of inflammatory cell death, likely plays a critical role in the development and progression of tumors. However, the relationship between pyroptosis-related genes (PRGs) and prognosis and immunity to PC is not entirely clear. This study, aimed at identifying the key PRGs in PC, highlights their prognostic value, immune characteristics, and candidate drugs for therapies. We screened 47 differentially expressed PRGs between PC and normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Afterwards, a pyroptosis-related gene prognostic index (PRGPI) was constructed based on eight PRGs (AIM2, GBP1, HMGB1, IL18, IRF6, NEK7, NLRP1 and PLCG1) selected by univariate and multivariate Cox regression analysis and LASSO regression analysis, and verified in two external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. We found that the PC patients in the PRGPI-defined subgroups not only reflected significantly different levels of infiltration in a variety of immune cells, such as M1 macrophages, but also showed differential expression in genes of the human leukocyte antigen (HLA) family and immune checkpoints. Additionally, molecular characteristics and drug sensitivity also stayed close to the PRGPI risk scores. Therefore, PRGPI may serve as a valuable prognostic biomarker and may potentially provide guidance toward novel therapeutic options for PC patients. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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Review

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31 pages, 863 KiB

Open AccessReview

The Tumor Immune Microenvironment in Primary CNS Neoplasms: A Review of Current Knowledge and Therapeutic Approaches

by Anita L. Kalluri, Pavan P. Shah and Michael Lim

Int. J. Mol. Sci. 2023, 24(3), 2020; https://doi.org/10.3390/ijms24032020 - 19 Jan 2023

Cited by 4 | Viewed by 2616

Abstract

Primary CNS neoplasms are responsible for considerable mortality and morbidity, and many therapies directed at primary brain tumors have proven unsuccessful despite their success in preclinical studies. Recently, the tumor immune microenvironment has emerged as a critical aspect of primary CNS neoplasms that may affect their malignancy, prognosis, and response to therapy across patients and tumor grades. This review covers the tumor microenvironment of various primary CNS neoplasms, with a focus on glioblastoma and meningioma. Additionally, current therapeutic strategies based on elements of the tumor microenvironment, including checkpoint inhibitor therapy and immunotherapeutic vaccines, are discussed. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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20 pages, 1737 KiB

Open AccessReview

Exposure of Immunogenic Tumor Antigens in Surrendered Immunity and the Significance of Autologous Tumor Cell-Based Vaccination in Precision Medicine

by Chiao-Hsu Ke, Yi-Han Chiu, Kuo-Chin Huang and Chen-Si Lin

Int. J. Mol. Sci. 2023, 24(1), 147; https://doi.org/10.3390/ijms24010147 - 21 Dec 2022

Cited by 3 | Viewed by 1959

Abstract

The mechanisms by which immune systems identify and destroy tumors, known as immunosurveillance, have been discussed for decades. However, several factors that lead to tumor persistence and escape from the attack of immune cells in a normal immune system have been found. In the process known as immunoediting, tumors decrease their immunogenicity and evade immunosurveillance. Furthermore, tumors exploit factors such as regulatory T cells, myeloid-derived suppressive cells, and inhibitory cytokines that avoid cytotoxic T cell (CTL) recognition. Current immunotherapies targeting tumors and their surroundings have been proposed. One such immunotherapy is autologous cancer vaccines (ACVs), which are characterized by enriched tumor antigens that can escalate specific CTL responses. Unfortunately, ACVs usually fail to activate desirable therapeutic effects, and the low immunogenicity of ACVs still needs to be elucidated. This difficulty highlights the significance of immunogenic antigens in antitumor therapies. Previous studies have shown that defective host immunity triggers tumor development by reprogramming tumor antigenic expressions. This phenomenon sheds new light on ACVs and provides a potential cue to improve the effectiveness of ACVs. Furthermore, synergistically with the ACV treatment, combinational therapy, which can reverse the suppressive tumor microenvironments, has also been widely proposed. Thus, in this review, we focus on tumor immunogenicity sculpted by the immune systems and discuss the significance and application of restructuring tumor antigens in precision medicine. Full article

(This article belongs to the Special Issue New Insights in Tumor Immunity)

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