Review
Cell Biology
Hong-Bo Li, Zi-Han Yang, Qing-Qu Guo
Summary: Pancreatic cancer is a highly malignant tumor with poor therapeutic outcomes, and immune checkpoint inhibitors have limited efficacy in treating PDAC due to its inhibitory immune microenvironment. Strategies to enhance the efficacy of ICIs in PDAC treatment by targeting the tumor microenvironment are currently being explored.
CELL COMMUNICATION AND SIGNALING
(2021)
Review
Immunology
Sophie Liot, Jonathan Balas, Alexandre Aubert, Laura Prigent, Perrine Mercier-Gouy, Bernard Verrier, Philippe Bertolino, Ana Hennino, Ulrich Valcourt, Elise Lambert
Summary: Pancreatic cancer, especially PDAC, has a poor prognosis with low survival rates, mainly due to its dense stroma deposition and immune suppression in the TME. Research on TME composition may lead to new therapeutic targets for better treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Eric M. Anderson, Shant Thomassian, Jun Gong, Andrew Hendifar, Arsen Osipov
Summary: Pancreatic cancer, with its highly immunosuppressive tumor microenvironment and dense stroma, presents challenges for traditional treatment approaches. Emerging treatment strategies have the potential to significantly improve outcomes for pancreatic cancer patients.
Review
Oncology
Jingchang Zhang, Renfeng Li, Shuai Huang
Summary: Pancreatic cancer has a high mortality rate due to the lack of early prognostic and diagnostic markers, and the interaction between pancreatic cancer cells, cancer stem cells, and the tumor microenvironment leads to chemoresistance. Precision treatment and targeted drugs are crucial for pancreatic cancer patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Robyn D. Gartrell, Thomas Enzler, Pan S. Kim, Benjamin T. Fullerton, Ladan Fazlollahi, Andrew X. Chen, Hanna E. Minns, Subha Perni, Stuart P. Weisberg, Emanuelle M. Rizk, Samuel Wang, Eun Jeong Oh, Xinzheng Guo, Codruta Chiuzan, Gulam A. Manji, Susan E. Bates, John Chabot, Beth Schrope, Michael Kluger, Jean Emond, Raul Rabadan, Donna Farber, Helen E. Remotti, David P. Horowitz, Yvonne M. Saenger
Summary: Despite complete surgical resection and intense systemic therapies, patients with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Immunotherapies have almost uniformly failed in the treatment of PDAC. This study found that while chemoradiation therapy (CRT) can achieve high T cell densities in PDAC compared to melanoma, the phenotype and spatial organization of T cells may limit the benefit of T cell infiltration in this immunotherapy-resistant tumor.
Review
Oncology
Yang Wu, Chun Zhang, Kuirong Jiang, Jens Werner, Alexandr V. Bazhin, Jan G. D'Haese
Summary: PDAC progression is influenced by PSCs, which through interactions with PCCs and other stroma cells, establish a tumor microenvironment that promotes tumor growth, metastasis, and chemoresistance. Targeting stroma has emerged as a promising strategy for PDAC therapy, with several novel strategies proposed to intervene in this complex crosstalk.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Maria Joao Amaral, Mariana Amaral, Joao Freitas, Rui Caetano Oliveira, Marco Serodio, Maria Augusta Cipriano, Jose Guilherme Tralhao
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, which accounts for 80% of its volume. The amount of stroma may affect prognosis, but its specific impact remains uncertain. This study aimed to investigate prognostic factors for PDAC patients undergoing surgery, including the impact of tumor stroma area (TSA). A retrospective study was conducted with PDAC patients who underwent surgical resection. TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa were identified as independent risk factors for mortality in PDAC patients undergoing surgery. Regarding TSA, a larger TSA seemed to be associated with longer overall survival (OS) for all stages. In stage II patients, a larger TSA was significantly associated with R0 resection, while in stage III patients, a larger TSA was significantly associated with a lower histological grade, higher preoperative AP levels, and lower preoperative AST levels. Patients with PDAC undergoing surgical resection and having preoperative CA19.9 > 500 U/L and AST >= 100 U/L had a higher risk of recurrence, although tumor stroma may have a protective effect in these patients.
Article
Oncology
Jiahong Jiang, Yaping Xu, Lianpeng Chang, Guoqing Ru, Xuefeng Xia, Ling Yang, Xin Yi, Zheling Chen, Dong-Sheng Huang, Liu Yang
Summary: This study revealed the presence of driver gene mutations in PDAC stroma, indicating that the genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and may help guide a more precise treatment paradigm in therapeutic options.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Azaz Ahmed, Rosa Klotz, Sophia Koehler, Nathalia Giese, Thilo Hackert, Christoph Springfeld, Dirk Jaeger, Niels Halama
Summary: This study investigated the immune features of the stroma in PDA patients, revealing a significant association of IL9 and IL18 with patient survival outcomes. IL9 was linked to an anti-tumoral cytokine network, while IL18 was associated with exhausted T cells. Patients with PDA showed higher serum levels of IL9 and lower levels of IL18 compared to healthy controls.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Tina Daunke, Silje Beckinger, Sascha Rahn, Sandra Kruger, Steffen Heckl, Heiner Schafer, Daniela Wesch, Christian Pilarsky, Markus Eckstein, Arndt Hartmann, Christoph Rocken, Anna Maxi Wandmacher, Susanne Sebens
Summary: In pancreatic ductal adenocarcinoma (PDAC), tumor-associated macrophages express PD-L1 while PDAC cells do not. PD-L1 expression is high at the tumor invasion front between tumor-associated macrophages and CD8+ T cells. Treatment with immune checkpoint inhibitors (ICI) does not enhance the activation and cytotoxicity of CD8+ T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Felix C. Popp, Ingracia Capino, Joana Bartels, Alexander I. Damanakis, Jiahui Li, Rabi R. Datta, Heike Loeser, Yue Zhao, Alexander Quaas, Philipp Lohneis, Christiane J. Bruns
Summary: Pancreatic cancer is highly resistant to immune checkpoint inhibitors. The potential of new immune molecules to restore the antitumor immune response was explored, with IDO expression associated with improved survival while VISTA, LAG3, and TIM3 expression were not correlated with survival. The study suggests that immune checkpoint inhibitors targeting VISTA, LAG3, and TIM3 may be inefficient in clinical application.
Article
Medicine, Research & Experimental
Song Han, Dongtao Fu, Gerik W. Tushoski, Lingsong Meng, Kelly M. Herremans, Andrea N. Riner, Thomas J. Geoge, Zhiguang Huo, Steven J. Hughes
Summary: This study explores the impact of tumor microenvironment heterogeneity on patient outcomes in pancreatic ductal adenocarcinoma (PDAC) at the single-cell level using mplxDSP technology. The results suggest that myofibroblasts adjacent to PDAC tumors overexpress certain genes, promoting adaptive immune response. The proximity of cancer-associated fibroblasts and leukocytes to the tumor significantly differs from those farther away, shedding light on the influence of microenvironment on immune tolerance.
Review
Oncology
Huey-Jen Lin, Yingguang Liu, Kailey Caroland, Jiayuh Lin
Summary: Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with a low 5-year survival rate. Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer and is associated with poor clinical outcomes. Scanty screening tools, abrupt metastasis, and chemoresistance contribute to the high mortality rate.
Article
Engineering, Biomedical
Jiangchao Wu, Xun Wang, Li Chen, Jianing Wang, Junlei Zhang, Jianghui Tang, Yongtao Ji, Jinyuan Song, Lin Wang, Yaxing Zhao, Hui Zhang, Taohong Li, Jianpeng Sheng, Dong Chen, Qi Zhang, Tingbo Liang
Summary: Reversing hypoxia in the tumor microenvironment using oxygen microcapsules is a potential strategy to improve the efficacy of immune checkpoint blockade for pancreatic ductal adenocarcinoma (PDAC). In in vivo experiments, oxygen microcapsules enhanced the effectiveness of immune checkpoint blockade on PDAC. Mechanistically, oxygen microcapsules could change the phenotype of tumor-associated macrophages and increase the proportion of cells involved in anti-tumor immune response.
BIOACTIVE MATERIALS
(2023)
Article
Oncology
Vincenzo Graziano, Andreas Dannhorn, Heather Hulme, Kate Williamson, Hannah Buckley, Saadia A. Karim, Matthew Wilson, Sheng Y. Lee, Brajesh P. Kaistha, Sabita Islam, James E. D. Thaventhiran, Frances M. Richards, Richard Goodwin, Rebecca Brais, Jennifer P. Morton, Simon J. Dovedi, Alwin G. Schuller, Jim Eyles, Duncan Jodrell
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to its ability to evade the immune system and resist immuno-oncology therapies (IOT) through the adenosine pathway, which generates extracellular adenosine (eAdo).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)