Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Scrutinizing the Soldiers and the Weapons in the Tumor Milieu

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

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 5480

Special Issue Editors


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Guest Editor
Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
Interests: pancreatic cancer; pancreatic ductal adenocarcinoma; tumor microenvironment
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Guest Editor
Unit of Internal Medicine “Guido Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
Interests: multiple myeloma; microenvironment; oncology; angiogenesis; hematology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is our pleasure to invite you to contribute to the upcoming Special Issue of the journal Cancers entitled “Immune Microenvironment in Pancreatic Ductal Adenocarcinoma: Scrutinizing the Soldiers and the Weapons in the Tumor Milieu”. The aim of this Special Issue is to provide an overview of current knowledge on the crucial mechanisms that promote tumor niche interactions and mediate immunosuppression during pancreatic cancer development and progression.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy of pancreatic cells, with a poor survival rate, when diagnosed in its advanced stage. Despite recent therapeutic advancements, disease progression remains mostly inevitable, and the disease is fatal in the majority of patients.

According to international guidelines, regional lymph nodes (LN) are not considered a surgery contraindication for the treatment of resectable PDAC. Nevertheless, the presence of LN metastases, as well as the number of positive LNs, strongly impact the PDAC outcome. Recently, the International Association of Pancreatology proposed to include the suspicion of regional LN metastases in the criteria that define borderline resectable PDAC. This frame of thinking affects a further selection of patients eligible for up-front surgery with the aim to reduce surgical morbidity and mortality in poor-prognosis patients. The scientific community is, in fact, now involved in identifying novel pathophysiologic drivers of tumor-invasiveness and prognostic factors for patient management and clinical decision-making. Recent developments in molecular profiling of PDAC have helped in achieving a better stratification of different clinical phenotypes, highlighting the possible role of genetic signatures in the LN metastatic process. Lymphatic dissemination depends on the interaction among cancer cells, the tumor immune microenvironment and the premetastatic niche. However, to date, no gene signature has been dissected in order to find a lymphatic-related metastasis driver in PDAC.

Thus, a major challenge in the treatment of patients with PDAC is the timely identification of treatment options in a personalized manner. Current approaches in precision oncology aim to match specific DNA mutations to drugs, but the incorporation of genome-wide RNA, DNA, epigenetics and proteomics profiles has not yet been clinically assessed.

All manuscripts will be peer-reviewed according to standard journal procedures and policies.

We hope that you will be able to accept this invitation and contribute to the success of this Special Issue. I look forward to collaborating with you.

Dr. Antonella Argentiero
Dr. Antonio G. Solimando
Guest Editors

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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.

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Keywords

  • pancreatic cancer
  • pancreatic ductal adenocarcinoma (PDAC)
  • immune microenvironment
  • tumor-invasiveness and prognostic factors
  • precision oncology
  • epigenetics
  • proteomics

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Published Papers (2 papers)

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Research

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17 pages, 10467 KiB  
Article
Anoikis-Related Gene Signature for Prognostication of Pancreatic Adenocarcinoma: A Multi-Omics Exploration and Verification Study
by Jin Zhang, Xuesong Li, Yi Lu, Guowen Wang and Ying Ma
Cancers 2023, 15(12), 3146; https://doi.org/10.3390/cancers15123146 - 11 Jun 2023
Cited by 7 | Viewed by 2338
Abstract
Anoikis, a form of apoptosis that occurs due to detachment of cells from the extracellular matrix, has been linked to the development of cancer in several studies. However, its role in pancreatic cancer remains incompletely understood. In this study, we utilized univariate Cox [...] Read more.
Anoikis, a form of apoptosis that occurs due to detachment of cells from the extracellular matrix, has been linked to the development of cancer in several studies. However, its role in pancreatic cancer remains incompletely understood. In this study, we utilized univariate Cox regression and LASSO regression analyses to establish a prognostic model for pancreatic adenocarcinoma based on anoikis-related genes in the TCGA database. Additionally, we performed univariate and multifactorial Cox analyses of protein expression results for TCGA pancreatic adenocarcinoma. We further explored the difference in immune infiltration between the high-risk and low-risk groups and verified the expression of the screened genes using quantitative real-time PCR (qRT-PCR). Our findings indicate that numerous anoikis-related genes are linked to pancreatic adenocarcinoma prognosis. We identified seven prognostic genes (MET, DYNLL2, CDK1, TNFSF10, PIP5K1C, MSLN, GKN1) and validated that their related proteins, such as EGFR and MMP2, have a significant impact on the prognosis of pancreatic adenocarcinoma. Based on clustering analyses of the seven prognostic genes, patients could be classified into three distinct categories, for which somatic mutations varied significantly across the groups. High-risk and low-risk groups also exhibited significant differences in immune infiltration. All genes were found to be highly expressed in pancreatic cancer cell lines (ASPC-1, CFPAC-1) as compared to a normal pancreatic cell line (HPDE). Based on the seven anoikis-related genes, we formulated a robust prognostic model with high predictive accuracy. We also identified the significant impact of KRAS, P53, and CDKN2A mutations on the prognosis of this fatal disease. Therefore, our study highlights the crucial role of anoikis in the development of the pancreatic adenocarcinoma tumor microenvironment. Full article
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Review

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17 pages, 741 KiB  
Review
Decoding the Intricate Landscape of Pancreatic Cancer: Insights into Tumor Biology, Microenvironment, and Therapeutic Interventions
by Antonella Argentiero, Alessandro Andriano, Ingrid Catalina Caradonna, Giulia de Martino and Vanessa Desantis
Cancers 2024, 16(13), 2438; https://doi.org/10.3390/cancers16132438 - 2 Jul 2024
Cited by 3 | Viewed by 2730
Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression and treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), contribute to tumor [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) presents significant oncological challenges due to its aggressive nature and poor prognosis. The tumor microenvironment (TME) plays a critical role in progression and treatment resistance. Non-neoplastic cells, such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), contribute to tumor growth, angiogenesis, and immune evasion. Although immune cells infiltrate TME, tumor cells evade immune responses by secreting chemokines and expressing immune checkpoint inhibitors (ICIs). Vascular components, like endothelial cells and pericytes, stimulate angiogenesis to support tumor growth, while adipocytes secrete factors that promote cell growth, invasion, and treatment resistance. Additionally, perineural invasion, a characteristic feature of PDAC, contributes to local recurrence and poor prognosis. Moreover, key signaling pathways including Kirsten rat sarcoma viral oncogene (KRAS), transforming growth factor beta (TGF-β), Notch, hypoxia-inducible factor (HIF), and Wnt/β-catenin drive tumor progression and resistance. Targeting the TME is crucial for developing effective therapies, including strategies like inhibiting CAFs, modulating immune response, disrupting angiogenesis, and blocking neural cell interactions. A recent multi-omic approach has identified signature genes associated with anoikis resistance, which could serve as prognostic biomarkers and targets for personalized therapy. Full article
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