Investigating Gametogenesis and Cancer for Discovering New Immunotherapeutic Targets

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

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 12105

Special Issue Editors


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Guest Editor
Department of Pathology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia
Interests: uropathology; perinatal pathology; placental pathology; electron microscopy; virtual and digital microscopy

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Guest Editor
Division of Hematology and Oncology, Texas Tech University Health Sciences Center, 3601 4th St STOP, 6591, Lubbock, TX 79430, USA
Interests: tumor immunology, developing therapeutic and preventive tumor vaccine; ovarian cancer, multiple myeloma, breast cancer, prostate cancer
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Special Issue Information

Dear Colleagues,

Human gametogenesis and carcinogenesis represent complex dynamic processes. Despite rapid advances in the fields of molecular and cellular biology, it is still widely debated as to how neoplastic cells progress through carcinogenesis and acquire their metastatic ability. Evidence has been accumulating since the middle of the last century—from animal models as well as from investigations in cancer patients—that the immune system can recognize and reject tumors. It is now accepted that immunotherapy evokes successful antitumor immune responses. Despite the increasing knowledge and preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as an alternative to traditional therapies for the treatment of cancer. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy remains limited by several factors. Among these is the paucity of tumor-associated antigens (TAAs) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. A family of TAAs called cancer-testis antigens (CTAs) has been identified, and several of their encoding genes have been investigated in cancer of unrelated histologic origin. A high number of CTAs have been found in the mammalian sperm flagellum. Furthermore, there is no consensus regarding how to prioritize neoantigens, and the lack of effective prediction models makes it difficult to predict clinical benefits.

Today, a wide selection of software and in silico tools are accessible to predict immunogenic neo-antigens, but each has its own strengths and weaknesses, and it has been problematic to identify which tools or which combinations of tools works best in the discovery of new targets.

This Special Issue will contain a collection of manuscripts that describe investigations into the different approaches of tumor immunotherapy, covering a range of model systems and tumor types. Latest research Articles and Reviews aiming to clarify concepts, interpret experimental data, indicate specific experiments, and categorize the rich body of knowledge on the basis of the similarities and/or shared behaviors of very different tumors are welcome.

Prof. Dr. Fabio Grizzi
Prof. Sanja Stifter
Prof. Dr. Maurizio Chiriva-Internati
Guest Editors

Manuscript Submission Information

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Keywords

  • tumor complexity
  • immunotherapy
  • tumor-associated antigens
  • gametogenesis
  • immuno-oncology
  • cancer heterogeneity
  • microenvironment
  • stromal remodeling
  • innate immunity
  • adaptive immunity
  • bioinformatics
  • artificial intelligence

Published Papers (3 papers)

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Research

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20 pages, 4998 KiB  
Article
Control of Cytoskeletal Dynamics by β-Arrestin1/Myosin Vb Signaling Regulates Endosomal Sorting and Scavenging Activity of the Atypical Chemokine Receptor ACKR2
by Alessandro Vacchini, Cinzia Cancellieri, Samantha Milanesi, Sabrina Badanai, Benedetta Savino, Francesco Bifari, Massimo Locati, Raffaella Bonecchi and Elena Monica Borroni
Vaccines 2020, 8(3), 542; https://doi.org/10.3390/vaccines8030542 - 17 Sep 2020
Cited by 8 | Viewed by 2978
Abstract
The atypical chemokine receptor ACKR2, formerly named D6, is a scavenger chemokine receptor with a non-redundant role in the control of inflammation and immunity. The scavenging activity of ACKR2 depends on its trafficking properties, which require actin cytoskeleton rearrangements downstream of a β-arrestin1-Rac1-PAK1-LIMK1-cofilin-dependent [...] Read more.
The atypical chemokine receptor ACKR2, formerly named D6, is a scavenger chemokine receptor with a non-redundant role in the control of inflammation and immunity. The scavenging activity of ACKR2 depends on its trafficking properties, which require actin cytoskeleton rearrangements downstream of a β-arrestin1-Rac1-PAK1-LIMK1-cofilin-dependent signaling pathway. We here demonstrate that in basal conditions, ACKR2 trafficking properties require intact actin and microtubules networks. The dynamic turnover of actin filaments is required to sustain ACKR2 constitutive endocytosis, while both actin and microtubule networks are involved in processes regulating ACKR2 constitutive sorting to rapid, Rab4-dependent and slow, Rab11-dependent recycling pathways, respectively. After chemokine engagement, ACKR2 requires myosin Vb activity to promote its trafficking from Rab11-positive recycling endosomes to the plasma membrane, which sustains its scavenging activity. Other than cofilin phosphorylation, induction of the β-arrestin1-dependent signaling pathway by ACKR2 agonists also leads to the rearrangement of microtubules, which is required to support the myosin Vb-dependent ACKR2 upregulation and its scavenging properties. Disruption of the actin-based cytoskeleton by the apoptosis-inducing agent staurosporine results in impaired ACKR2 internalization and chemokine degradation that is consistent with the emerging scavenging-independent activity of the receptor in apoptotic neutrophils instrumental for promoting efficient efferocytosis during the resolution of inflammation. In conclusion, we provide evidence that ACKR2 activates a β-arrestin1-dependent signaling pathway, triggering both the actin and the microtubule cytoskeletal networks, which control its trafficking and scavenger properties. Full article
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Review

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18 pages, 7517 KiB  
Review
Crosstalk between Stress Granules, Exosomes, Tumour Antigens, and Immune Cells: Significance for Cancer Immunity
by Vinoth Kumar Kothandan, Sangeetha Kothandan, Do Hee Kim, Youngro Byun, Yong-kyu Lee, In-Kyu Park and Seung Rim Hwang
Vaccines 2020, 8(2), 172; https://doi.org/10.3390/vaccines8020172 - 8 Apr 2020
Cited by 11 | Viewed by 4413
Abstract
RNA granules and exosomes produced by tumour cells under various stresses in the microenvironment act as critical determinants of cell survival by promoting angiogenesis, cancer metastasis, chemoresistance, and immunosuppression. Meanwhile, developmental cancer/testis (CT) antigens that are normally sequestered in male germ cells of [...] Read more.
RNA granules and exosomes produced by tumour cells under various stresses in the microenvironment act as critical determinants of cell survival by promoting angiogenesis, cancer metastasis, chemoresistance, and immunosuppression. Meanwhile, developmental cancer/testis (CT) antigens that are normally sequestered in male germ cells of the testes, but which are overexpressed in malignant tumour cells, can function as tumour antigens triggering immune responses. As CT antigens are potential vaccine candidates for use in cancer immunotherapy, they could be targeted together with crosstalk between stress granules, exosomes, and immune cells for a synergistic effect. In this review, we describe the effects of exosomes and exosomal components presented to the recipient cells under different types of stresses on immune cells and cancer progression. Furthermore, we discuss their significance for cancer immunity, as well as the outlook for their future application. Full article
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25 pages, 2117 KiB  
Review
New Insights on the Emerging Genomic Landscape of CXCR4 in Cancer: A Lesson from WHIM
by Stefania Scala, Crescenzo D’Alterio, Samantha Milanesi, Alessandra Castagna, Roberta Carriero, Floriana Maria Farina, Massimo Locati and Elena Monica Borroni
Vaccines 2020, 8(2), 164; https://doi.org/10.3390/vaccines8020164 - 3 Apr 2020
Cited by 11 | Viewed by 4163
Abstract
Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective [...] Read more.
Deciphering the molecular alterations leading to disease initiation and progression is currently crucial to identify the most relevant targets for precision therapy in cancer patients. Cancers express a complex chemokine network influencing leucocyte infiltration and angiogenesis. Moreover, malignant cells also express a selective repertoire of chemokine receptors that sustain their growth and spread. At present, different cancer types have been shown to overexpress C-X-C chemokine receptor type 4 (CXCR4) and to respond to its ligand C-X-C motif chemokine 12 (CXCL12). The CXCL12/CXCR4 axis influences cancer biology, promoting survival, proliferation, and angiogenesis, and plays a pivotal role in directing migration of cancer cells to sites of metastases, making it a prognostic marker and a therapeutic target. More recently, mutations in the C-terminus of CXCR4 have been identified in the genomic landscape of patients affected by Waldenstrom’s macroglobulinemia, a rare B cell neoplasm. These mutations closely resemble those occurring in Warts, Hypogammaglobulinemia, Immunodeficiency, and Myelokathexis (WHIM) syndrome, an immunodeficiency associated with CXCR4 aberrant expression and activity and with chemotherapy resistance in clinical trials. In this review, we summarize the current knowledge on the relevance of CXCR4 mutations in cancer biology, focusing on its importance as predictors of clinical presentation and response to therapy. Full article
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