Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut atnd Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. +MORE
Yong Chan Lee |
Professor of Medicine Director, Gastrointestinal Research Laboratory Veterans Affairs Medical Center, Univ. California San Francisco San Francisco, USA |
Jong Pil Im | Seoul National University College of Medicine, Seoul, Korea |
Robert S. Bresalier | University of Texas M. D. Anderson Cancer Center, Houston, USA |
Steven H. Itzkowitz | Mount Sinai Medical Center, NY, USA |
All papers submitted to Gut and Liver are reviewed by the editorial team before being sent out for an external peer review to rule out papers that have low priority, insufficient originality, scientific flaws, or the absence of a message of importance to the readers of the Journal. A decision about these papers will usually be made within two or three weeks.
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Chae Yoon Lim1 , Jae Hyuck Chang2
, Won Sun Lee1
, Jeana Kim3
, and Il Young Park4
Correspondence to:Jae Hyuck Chang
ORCID https://orcid.org/0000-0003-1180-2693
E-mail wwjjaang@catholic.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gut Liver
Published online December 21, 2021
Copyright © Gut and Liver.
Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma.
Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures.
Results: CD163+ (predominant in M2 macrophages) and FOXP3+ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163+ expression had shorter overall survival than those with low CD163+ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR+ (predominant in M1 macrophages) and a decrease in CD163+ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR+ and decrease CD163+ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis.
Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.
Keywords: CD40 immunoglobulin, CD163 antigen, Macrophages, Pancreatic neoplasm, Tumor microenvironment
Gut and Liver
Published online December 21, 2021
Copyright © Gut and Liver.
Chae Yoon Lim1 , Jae Hyuck Chang2
, Won Sun Lee1
, Jeana Kim3
, and Il Young Park4
1Institute of Clinical Medicine Research, Departments of 2Internal Medicine, 3Hospital Pathology, and 4Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
Correspondence to:Jae Hyuck Chang
ORCID https://orcid.org/0000-0003-1180-2693
E-mail wwjjaang@catholic.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background/Aims: CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma.
Methods: Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures.
Results: CD163+ (predominant in M2 macrophages) and FOXP3+ (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163+ expression had shorter overall survival than those with low CD163+ expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR+ (predominant in M1 macrophages) and a decrease in CD163+ expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR+ and decrease CD163+ expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis.
Conclusions: CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.
Keywords: CD40 immunoglobulin, CD163 antigen, Macrophages, Pancreatic neoplasm, Tumor microenvironment