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Cancers
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Immunotherapy: New Prospective in the Treatment of Ovarian Cancer
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Immunotherapy: New Prospective in the Treatment of Ovarian Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 27011

Special Issue Editors

Dr. Chiara Napoletano

E-Mail Website
Guest Editor
Department of Experimental Medicine, “Sapienza” University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
Interests: translational research; immunotherapy; vaccination; dendritic cells; ovarian cancer; solid tumors
Prof. Dr. Filippo Bellati

E-Mail Website
Guest Editor
Department of Gynecology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
Interests: gynecology and obstetrics; gynecologic oncology; minimally invasive surgery

Special Issue Information

Dear Colleagues, 

Ovarian cancer still remains the major unresolved problem of gynaecologic oncologists in terms of efficient treatment. Despite the fact that in the last years, an increasing number of women have benefited from prolonged survival thanks to surgical management and the introduction of new therapeutic strategies, over 70% of patients relapse and only 47% of them survive more than 5 years.

Due to the great importance that immunological fitness has in the clinical outcome, large efforts have been made to develop new immunotherapeutic strategies to be administered alone or in combination with standard therapies. Several studies have showed promising results in the generation of specific anti-tumor T cell response, but with minimal clinical benefit. The great heterogeneity observed in ovarian cancer tissues, the high grade of the immunosuppression of the tumor microenvironment, and the compromised status of the immune fitness of patients enrolled in these studies have severely influenced the success rate. In addition to the development of novel immunotherapy approaches, several questions that could impact the long-term results of any immunological intervention need further investigation. Timing of immunological treatment and integration with the several currently adopted therapeutic strategies and drug administration approaches (administration schedule, intravenous vs intraperitoneal vs intranodal, dosage, etc.) represent critical issues that need to be resolved. 

This Special Issue is focused on novel therapeutic strategies (immunotherapy alone or combined with standard therapies or other agents), innovative administration schedule, new immune targets, novel ideas and approaches to further improve the therapeutic efficacy of immunotherapy.

Prof. Chiara Napoletano
Prof. Filippo Bellati
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. Cancers is an international peer-reviewed open access semimonthly 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 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

  • ovarian cancer
  • immunotherapy
  • immune checkpoint inhibitors
  • PARP inhibitors
  • vaccination
  • antigens
  • targeted therapy
  • adoptive T cell therapy
  • combination immunotherapies
  • immunomodulatory agents

Published Papers (7 papers)

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Research

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22 pages, 4955 KiB  
Article
Macrophages Impair TLR9 Agonist Antitumor Activity through Interacting with the Anti-PD-1 Antibody Fc Domain
by Simone Camelliti, Valentino Le Noci, Francesca Bianchi, Chiara Storti, Francesca Arnaboldi, Alessandra Cataldo, Serena Indino, Elena Jachetti, Mariangela Figini, Mario Paolo Colombo, Andrea Balsari, Nicoletta Gagliano, Elda Tagliabue, Lucia Sfondrini and Michele Sommariva
Cancers 2021, 13(16), 4081; https://doi.org/10.3390/cancers13164081 - 13 Aug 2021
Cited by 7 | Viewed by 2766
Abstract
Background. A combination of TLR9 agonists and an anti-PD-1 antibody has been reported to be effective in immunocompetent mice but the role of innate immunity has not yet been completely elucidated. Therefore, we investigated the contribution of the innate immune system to this [...] Read more.
Background. A combination of TLR9 agonists and an anti-PD-1 antibody has been reported to be effective in immunocompetent mice but the role of innate immunity has not yet been completely elucidated. Therefore, we investigated the contribution of the innate immune system to this combinatorial immunotherapeutic regimens using an immunodeficient mouse model in which the effector functions of innate immunity can clearly emerge without any interference from T lymphocytes. Methods. Athymic mice xenografted with IGROV-1 human ovarian cells, reported to be sensitive to TLR9 agonist therapy, were treated with cytosine–guanine (CpG)-oligodeoxynucleotides (ODNs), an anti-PD-1 antibody or their combination. Results. We found that PD-1 blockade dampened CpG-ODN antitumor activity. In vitro studies indicated that the interaction between the anti-PD-1 antibody fragment crystallizable (Fc) domain and macrophage Fc receptors caused these immune cells to acquire an immunoregulatory phenotype, contributing to a decrease in the efficacy of CpG-ODNs. Accordingly, in vivo macrophage depletion abrogated the detrimental effect exerted by the anti-PD-1 antibody. Conclusion. Our data suggest that if TLR signaling is active in macrophages, coadministration of an anti-PD-1 antibody can reprogram these immune cells towards a polarization state able to negatively affect the immune response and eventually promote tumor growth. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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19 pages, 3403 KiB  
Article
Identification of a Novel Tumor Microenvironment Prognostic Signature for Advanced-Stage Serous Ovarian Cancer
by Mingjun Zheng, Junyu Long, Anca Chelariu-Raicu, Heather Mullikin, Theresa Vilsmaier, Aurelia Vattai, Helene Hildegard Heidegger, Falk Batz, Simon Keckstein, Udo Jeschke, Fabian Trillsch, Sven Mahner and Till Kaltofen
Cancers 2021, 13(13), 3343; https://doi.org/10.3390/cancers13133343 - 3 Jul 2021
Cited by 14 | Viewed by 3310
Abstract
(1) Background: The tumor microenvironment is involved in the growth and proliferation of malignant tumors and in the process of resistance towards systemic and targeted therapies. A correlation between the gene expression profile of the tumor microenvironment and the prognosis of ovarian cancer [...] Read more.
(1) Background: The tumor microenvironment is involved in the growth and proliferation of malignant tumors and in the process of resistance towards systemic and targeted therapies. A correlation between the gene expression profile of the tumor microenvironment and the prognosis of ovarian cancer patients is already known. (2) Methods: Based on data from The Cancer Genome Atlas (379 RNA sequencing samples), we constructed a prognostic 11-gene signature (SNRPA1, CCL19, CXCL11, CDC5L, APCDD1, LPAR2, PI3, PLEKHF1, CCDC80, CPXM1 and CTAG2) for Fédération Internationale de Gynécologie et d’Obstétrique stage III and IV serous ovarian cancer through lasso regression. (3) Results: The established risk score was able to predict the 1-, 3- and 5-year prognoses more accurately than previously known models. (4) Conclusions: We were able to confirm the predictive power of this model when we applied it to cervical and urothelial cancer, supporting its pan-cancer usability. We found that immune checkpoint genes correlate negatively with a higher risk score. Based on this information, we used our risk score to predict the biological response of cancer samples to an anti-programmed death ligand 1 immunotherapy, which could be useful for future clinical studies on immunotherapy in ovarian cancer. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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20 pages, 2918 KiB  
Article
Investigating Patterns of Immune Interaction in Ovarian Cancer: Probing the O-glycoproteome by the Macrophage Galactose-Like C-Type Lectin (MGL)
by Chiara Napoletano, Catharina Steentoff, Federico Battisti, Zilu Ye, Hassan Rahimi, Ilaria Grazia Zizzari, Marco Dionisi, Bruna Cerbelli, Federica Tomao, Deborah French, Giulia d’Amati, Pierluigi Benedetti Panici, Sergey Vakhrushev, Henrik Clausen, Marianna Nuti and Aurelia Rughetti
Cancers 2020, 12(10), 2841; https://doi.org/10.3390/cancers12102841 - 1 Oct 2020
Cited by 9 | Viewed by 3059
Abstract
Glycosylation, the posttranslational linking of sugar molecules to proteins, is notoriously altered during tumor transformation. More specifically in carcinomas, GalNAc-type O-glycosylation, is characterized by biosynthetically immature truncated glycans present on the cancer cell surface, which profoundly impact anti-tumor immune recognition. The tumor-associated [...] Read more.
Glycosylation, the posttranslational linking of sugar molecules to proteins, is notoriously altered during tumor transformation. More specifically in carcinomas, GalNAc-type O-glycosylation, is characterized by biosynthetically immature truncated glycans present on the cancer cell surface, which profoundly impact anti-tumor immune recognition. The tumor-associated glycan pattern may thus be regarded as a biomarker of immune modulation. In epithelial ovarian cancer (EOC) there is a particular lack of specific biomarkers and molecular targets to aid early diagnosis and develop novel therapeutic interventions. The aim of this study was to investigate the ovarian cancer O-glycoproteome and identify tumor-associated glycoproteins relevant in tumor–dendritic cell (DC) interactions, mediated by macrophage galactose-like C type lectin (MGL), which recognizes the tumor-associated Tn O-glycan. Lectin weak affinity chromatography (LWAC) was employed to probe the O-glycopeptidome by MGL and Vicia villosa agglutinin (VVA) lectin using glycoengineered ovarian cancer cell lines and ovarian cancer tissues as input material. Biochemical and bioinformatics analysis gave information on the glycan arrangement recognized by MGL in tumor cells. The potential MGL binders identified were located, as expected, at the cell membrane, but also within the intracellular compartment and the matrisome, suggesting that MGL in vivo may play a complex role in sensing microenvironmental cues. The tumor glycoproteins binders for MGL may become relevant to characterize the interaction between the immune system and tumor progression and contribute to the design of glycan targeting-based strategies for EOC immunotherapeutic interventions. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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Review

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22 pages, 1140 KiB  
Review
Chasing Immune Checkpoint Inhibitors in Ovarian Cancer: Novel Combinations and Biomarker Discovery
by Ilaria Colombo, Katherine Karakasis, Sneha Suku and Amit M. Oza
Cancers 2023, 15(12), 3220; https://doi.org/10.3390/cancers15123220 - 16 Jun 2023
Cited by 10 | Viewed by 3343
Abstract
A deep understanding of the tumor microenvironment and the recognition of tumor-infiltrating lymphocytes as a prognostic factor have resulted in major milestones in immunotherapy that have led to therapeutic advances in treating many cancers. Yet, the translation of this knowledge to clinical success [...] Read more.
A deep understanding of the tumor microenvironment and the recognition of tumor-infiltrating lymphocytes as a prognostic factor have resulted in major milestones in immunotherapy that have led to therapeutic advances in treating many cancers. Yet, the translation of this knowledge to clinical success for ovarian cancer remains a challenge. The efficacy of immune checkpoint inhibitors as single agents or combined with chemotherapy has been unsatisfactory, leading to the exploration of alternative combination strategies with targeted agents (e.g., poly-ADP-ribose inhibitors (PARP)and angiogenesis inhibitors) and novel immunotherapy approaches. Among the different histological subtypes, clear cell ovarian cancer has shown a higher sensitivity to immunotherapy. A deeper understanding of the mechanism of immune resistance within the context of ovarian cancer and the identification of predictive biomarkers remain central discovery benchmarks to be realized. This will be critical to successfully define the precision use of immune checkpoint inhibitors for the treatment of ovarian cancer. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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34 pages, 1044 KiB  
Review
Integrating Cancer Vaccines in the Standard-of-Care of Ovarian Cancer: Translating Preclinical Models to Human
by Cheryl Lai-Lai Chiang, Raphaël Rovelli, Apostolos Sarivalasis and Lana E. Kandalaft
Cancers 2021, 13(18), 4553; https://doi.org/10.3390/cancers13184553 - 10 Sep 2021
Cited by 6 | Viewed by 3136
Abstract
As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC [...] Read more.
As the majority of ovarian cancer (OC) patients are diagnosed with metastatic disease, less than 40% will survive past 5 years after diagnosis. OC is characterized by a succession of remissions and recurrences. The most promising time point for immunotherapeutic interventions in OC is following debulking surgery. Accumulating evidence shows that T cells are important in OC; thus, cancer vaccines capable of eliciting antitumor T cells will be effective in OC treatment. In this review, we discuss different cancer vaccines and propose strategies for their incorporation into the OC standard-of-care regimens. Using the murine ID8 ovarian tumor model, we provide evidence that a cancer vaccine can be effectively combined with OC standard-of-care to achieve greater overall efficacy. We demonstrate several important similarities between the ID8 model and OC patients, in terms of response to immunotherapies, and the ID8 model can be an important tool for evaluating combinatorial regimens and clinical trial designs in OC. Other emerging models, including patient-derived xenograft and genetically engineered mouse models, are continuing to improve and can be useful for evaluating cancer vaccination therapies in the near future. Here, we provide a comprehensive review of the completed and current clinical trials evaluating cancer vaccines in OC. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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17 pages, 735 KiB  
Review
Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives
by Brigida Anna Maiorano, Mauro Francesco Pio Maiorano, Domenica Lorusso and Evaristo Maiello
Cancers 2021, 13(17), 4438; https://doi.org/10.3390/cancers13174438 - 3 Sep 2021
Cited by 45 | Viewed by 5315
Abstract
Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based [...] Read more.
Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in OC. Methods: We searched PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were identified, of which 16 were phase I or II and 4 phase III trials. These trials used ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, aterolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab). There was no reported improvement in survival, and some trials were terminated early due to toxicity or lack of response. Combining ICIs with chemotherapy, anti-VEGF therapy, or PARP inhibitors improved response rates and survival in spite of a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of OC might lead to better treatment options and facilitate the design of tailored trials. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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13 pages, 1936 KiB  
Review
Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors
by Camilla Nero, Francesca Ciccarone, Antonella Pietragalla, Simona Duranti, Gennaro Daniele, Vanda Salutari, Maria Vittoria Carbone, Giovanni Scambia and Domenica Lorusso
Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298 - 15 Mar 2021
Cited by 23 | Viewed by 5159
Abstract
Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) [...] Read more.
Ovarian cancer treatment strategy is mainly based on three pillars: cytoreductive surgery, platinum-based chemotherapy, and targeted therapies. The latter in the last decade has provided a remarkable improvement in progression free patients and, hopefully, in overall survival. In particular, poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors exploit BRCA 1/2 mutations and DNA damage response deficiencies, which are believed to concern up to 50% of high grade epithelial ovarian cancer cases. While these agents have an established role in ovarian cancer treatment strategy in BRCA mutated and homologous recombination deficient patients, an appropriate predictive molecular test to select patients is lacking in clinical practice. At the same time, the impressive results of immunotherapy in other malignancies, have opened the space for the introduction of immune-stimulatory drugs in ovarian cancer. Despite immune checkpoint inhibitors as a monotherapy bringing only modest efficacy when assessed in pretreated ovarian cancer patients, the combination with chemotherapy, anti-angiogenetics, PARP inhibitors, and radiotherapy is believed to warrant further investigation. We reviewed literature evidence on PARP inhibitors and immunotherapy in ovarian cancer treatment. Full article
(This article belongs to the Special Issue Immunotherapy: New Prospective in the Treatment of Ovarian Cancer)
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