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The Tumor Microenvironment and Immune System in Biliopancreatic Cancers

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 7846

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Special Issue Editors

Dr. Paola Parente

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Guest Editor

Unit of Pathology, Fondazione IRCCS Ospedale “Casa Sollievo della Sofferenza”, Viale Cappuccini 1, 71013 San Giovanni Rotondo, Italy
Interests: gastro-intestinal cancer; bilio-pancreatic cancer; IBD; celiac disease; histopathology; immunohistochemistry; hematopathology
Special Issues, Collections and Topics in MDPI journals

Dr. Guido Giordano

E-Mail Website
Guest Editor

Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy
Interests: oncology; molecular biology; cell biology; pancreatic cancer; colorectal cancer; gastric cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biliopancreatic cancers (BPC) are lethal and aggressive diseases. The majority of patients have unresectable, locally advanced, or metastatic disease at the time of diagnosis. The tumor stroma and microenvironment, along with the immune system, play a crucial role in tumor aggressiveness, and the relationship among these components may lead to therapy resistance. These factors have recently been addressed as potential targets for new drug development in BPC tumors, even if little is known about their crosstalk. Major guidelines suggest the use of immune-checkpoint inhibitors in unresectable or metastatic gastrointestinal cancers with high microsatellite instability (MSI-H). However, BPC, MSI-H patients represent only a very small proportion, accounting for less than 4%.

The aim of this Special Issue is to collect papers (original articles and full reviews) on the following specific topics:

Molecular profile of epithelial and non-epithelial (tumor stroma and tumor microenvironment) components of BPC
Biological or molecular evidence concerning the use of immunotherapy in BPC
New and promising tissue/circulating molecular markers of response/resistance to therapies in BPC
Molecular basis for novel treatment combinations targeting both the immune system and the tumor microenvironment

Dr. Paola Parente
Dr. Guido Giordano
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. 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 microenvironment
immune system
immune-checkpoint inhibitors
immunotherapy
target therapy
biomarker
pancreatic cancer
biliary tract tumors

Published Papers (3 papers)

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Research

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15 pages, 1997 KiB

Open AccessArticle

A Cross-Sectional and Longitudinal Analysis of Pre-Diagnostic Blood Plasma Biomarkers for Early Detection of Pancreatic Cancer

by James Mason, Erik Lundberg, Pär Jonsson, Hanna Nyström, Oskar Franklin, Christina Lundin, Peter Naredi, Henrik Antti, Malin Sund and Daniel Öhlund

Int. J. Mol. Sci. 2022, 23(21), 12969; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232112969 - 26 Oct 2022

Cited by 3 | Viewed by 2311

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC. Full article

(This article belongs to the Special Issue The Tumor Microenvironment and Immune System in Biliopancreatic Cancers)

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17 pages, 4687 KiB

Open AccessArticle

Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer

by Jingwei Shi, Xiao Shen, Qi Kang, Xing Yang, Maximilian Denzinger, Marko Kornmann and Benno Traub

Int. J. Mol. Sci. 2022, 23(7), 3659; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23073659 - 26 Mar 2022

Cited by 3 | Viewed by 2033

Abstract

In search of new therapies for pancreatic cancer, cytokine pathways have attracted increasing interest in recent years. Cytokines play a vital role in the crosstalk between tumour cells and the tumour microenvironment. The related inflammatory cytokines IL-4 and IL-13 can regularly be detected at increased levels in the microenvironment of pancreatic cancer. They share a receptor heterodimer consisting of IL-4Rα and IL-13Rα1. While IL-4Rα induces a more oncogenic phenotype, the role of IL-13Rα1 was yet to be determined. ShRNA-based knockdown of IL-13Rα1 was performed in Capan-1 and MIA PaCa-2. We assessed cell growth and migratory capacities under the influence of IL-13Rα1. Pathway alterations were detected by immunoblot analysis. We now have demonstrated that the loss of IL-13Rα1 induces apoptosis in pancreatic cancer cells. This was associated with an epithelial-to-mesenchymal transition. Loss of IL-13Rα1 also abolished the effects of exogenous IL-4 and IL-13 stimulation. Interestingly, in wild type cells, cytokine stimulation caused a similar increase in migratory capacities as after IL-13Rα1 knockdown. Overall, our results indicate the vital role of IL-13Rα1 in the progression of pancreatic cancer. The differential expression of IL-4Rα and IL-13Rα1 has to be taken into account when considering a cytokine-targeted therapy in pancreatic cancer. Full article

(This article belongs to the Special Issue The Tumor Microenvironment and Immune System in Biliopancreatic Cancers)

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Review

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18 pages, 731 KiB

Open AccessReview

Immunotherapy for Biliary Tract Cancer in the Era of Precision Medicine: Current Knowledge and Future Perspectives

by Davide Ciardiello, Brigida Anna Maiorano, Paola Parente, Maria Grazia Rodriquenz, Tiziana Pia Latiano, Cinzia Chiarazzo, Valerio Pazienza, Luigi Pio Guerrera, Brunella Amoruso, Nicola Normanno, Giulia Martini, Fortunato Ciardiello, Erika Martinelli and Evaristo Maiello

Int. J. Mol. Sci. 2022, 23(2), 820; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020820 - 13 Jan 2022

Cited by 16 | Viewed by 2859

Abstract

Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response. Full article

(This article belongs to the Special Issue The Tumor Microenvironment and Immune System in Biliopancreatic Cancers)

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