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Cancers
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Immune Response and Immunotherapy in Bladder Cancer
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Immune Response and Immunotherapy in Bladder Cancer

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 7431

Special Issue Editors

Dr. Alfredo Minguela

E-Mail Website
Guest Editor
Clinic University Hospital Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 El Palmar Murcia, Spain
Interests: bladder cancer; innate and adaptive immune responses; immunotherapy; bacille Calmette–Guerin
Dr. Pedro López-Cubillana

E-Mail Website
Guest Editor
Clinic University Hospital Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 El Palmar Murcia, Spain
Interests: bladder cancer; innate and adaptive immune responses; immunotherapy; bacille Calmette–Guerin

Special Issue Information

Dear Colleagues,

Bladder cancer represents a wide spectrum of diseases, ranging from recurrent noninvasive tumors to those at aggressive or advanced stages that require intensive treatments. Bladder cancer accounts for an estimated 500,000 new cases and 200,000 deaths yearly worldwide. Understanding the underlying biology of bladder cancer has changed how this disease is diagnosed and treated. Bladder cancer is highly immunogenic, involving innate and adaptive components of the immune system. Although little is still known of how immune cells respond to bladder cancer, immunotherapy with the bacille Calmette–Guerin (BCG) remains the gold standard in non-muscle invasive bladder cancer. In addition, the use of immunotherapy to block immune checkpoints (anti-CTLA4 and anto-PD1/PD-L1) used to boost natural immune vigilance is emerging as an effective therapy in invasive and metastatic urologic tumors. This Special Issue aims to unravel the immune responses involving innate and adaptive immune cells in bladder cancer that will contribute to establishing new and promising therapeutic options, while reviewing the immunotherapies currently in use in bladder cancer.

Dr. Alfredo Minguela
Dr. Pedro López-Cubillana
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 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

  • bladder cancer
  • innate and adaptive immune responses
  • immunotherapy
  • bacille Calmette–Guerin

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Published Papers (2 papers)

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Research

23 pages, 5851 KiB  
Article
Toward Tumor Fight and Tumor Microenvironment Remodeling: PBA Induces Cell Cycle Arrest and Reduces Tumor Hybrid Cells’ Pluripotency in Bladder Cancer
by Carolina Rubio, José Avendaño-Ortiz, Raquel Ruiz-Palomares, Viktoriya Karaivanova, Omaira Alberquilla, Rebeca Sánchez-Domínguez, José Carlos Casalvilla-Dueñas, Karla Montalbán-Hernández, Iris Lodewijk, Marta Rodríguez-Izquierdo, Ester Munera-Maravilla, Sandra P. Nunes, Cristian Suárez-Cabrera, Miriam Pérez-Crespo, Víctor G. Martínez, Lucía Morales, Mercedes Pérez-Escavy, Miguel Alonso-Sánchez, Roberto Lozano-Rodríguez, Francisco J. Cueto, Luis A. Aguirre, Félix Guerrero-Ramos, Jesús M. Paramio, Eduardo López-Collazo and Marta Dueñasadd Show full author list remove Hide full author list
Cancers 2022, 14(2), 287; https://doi.org/10.3390/cancers14020287 - 7 Jan 2022
Cited by 9 | Viewed by 3616
Abstract
Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of Bacillus Calmette–Guérin (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some [...] Read more.
Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of Bacillus Calmette–Guérin (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some patients cannot be treated with this therapy due to comorbidities and severe inflammatory side effects. The overexpression of histone deacetylases (HDACs) in BC has been correlated with macrophage polarization together with higher tumor grades and poor prognosis. Herein we demonstrated that phenylbutyrate acid (PBA), a HDAC inhibitor, acts as an antitumoral compound and immunomodulator. In BC cell lines, PBA induced significant cell cycle arrest in G1, reduced stemness markers and increased PD-L1 expression with a corresponding reduction in histone 3 and 4 acetylation patterns. Concerning its role as an immunomodulator, we found that PBA reduced macrophage IL-6 and IL-10 production as well as CD14 downregulation and the upregulation of both PD-L1 and IL-1β. Along this line, PBA showed a reduction in IL-4-induced M2 polarization in human macrophages. In co-cultures of BC cell lines with human macrophages, a double-positive myeloid–tumoral hybrid population (CD11b+EPCAM+) was detected after 48 h, which indicates BC cell–macrophage fusions known as tumor hybrid cells (THC). These THC were characterized by high PD-L1 and stemness markers (SOX2, NANOG, miR-302) as compared with non-fused (CD11b−EPCAM+) cancer cells. Eventually, PBA reduced stemness markers along with BMP4 and IL-10. Our data indicate that PBA could have beneficial properties for BC management, affecting not only tumor cells but also the TME. Full article
(This article belongs to the Special Issue Immune Response and Immunotherapy in Bladder Cancer)
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13 pages, 2262 KiB  
Article
Whole Blood Transcriptome Profiling Identifies DNA Replication and Cell Cycle Regulation as Early Marker of Response to Anti-PD-1 in Patients with Urothelial Cancer
by Sandra van Wilpe, Victoria Wosika, Laura Ciarloni, Sahar Hosseinian Ehrensberger, Rachel Jeitziner, Paolo Angelino, Tjitske Duiveman-de Boer, Rutger H. T. Koornstra, I. Jolanda M. de Vries, Winald R. Gerritsen, Jack Schalken and Niven Mehra
Cancers 2021, 13(18), 4660; https://doi.org/10.3390/cancers13184660 - 17 Sep 2021
Cited by 2 | Viewed by 2815
Abstract
Although immune checkpoint inhibitors improve median overall survival in patients with metastatic urothelial cancer (mUC), only a minority of patients benefit from it. Early blood-based response biomarkers may provide a reliable way to assess response weeks before imaging is available, enabling an early [...] Read more.
Although immune checkpoint inhibitors improve median overall survival in patients with metastatic urothelial cancer (mUC), only a minority of patients benefit from it. Early blood-based response biomarkers may provide a reliable way to assess response weeks before imaging is available, enabling an early switch to other therapies. We conducted an exploratory study aimed at the identification of early markers of response to anti-PD-1 in patients with mUC. Whole blood RNA sequencing and phenotyping of peripheral blood mononuclear cells were performed on samples of 26 patients obtained before and after 2 to 6 weeks of anti-PD-1. Between baseline and on-treatment samples of patients with clinical benefit, 51 differentially expressed genes (DEGs) were identified, of which 37 were upregulated during treatment. Among the upregulated genes was PDCD1, the gene encoding PD-1. STRING network analysis revealed a cluster of five interconnected DEGs which were all involved in DNA replication or cell cycle regulation. We hypothesized that the upregulation of DNA replication/cell cycle genes is a result of T cell proliferation and we were able to detect an increase in Ki-67+ CD8+ T cells in patients with clinical benefit (median increase: 1.65%, range −0.63 to 7.06%, p = 0.012). In patients without clinical benefit, no DEGs were identified and no increase in Ki-67+ CD8+ T cells was observed. In conclusion, whole blood transcriptome profiling identified early changes in DNA replication and cell cycle regulation genes as markers of clinical benefit to anti-PD-1 in patients with urothelial cancer. Although promising, our findings require further validation before implementation in the clinic. Full article
(This article belongs to the Special Issue Immune Response and Immunotherapy in Bladder Cancer)
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