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Literature DB >> 31362079

Inhibiting PI3 kinase-γ in both myeloid and plasma cells remodels the suppressive tumor microenvironment in desmoplastic tumors.

Xueqiong Zhang¹, Limei Shen², Qi Liu², Lin Hou², Leaf Huang³.

Abstract

Phosphoinositide-3-kinases (PI3Ks) are part of signal transducing enzymes that mediate key cellular functions in cancer and immunity. PI3K-γ is crucial for cellular activation and migration in response to certain chemokines. PI3K-γ is highly expressed in myeloid cells and promotes their migration and the production of inflammatory mediators. We found that PI3K-γ was also highly expressed in tumor-associated B cells. IPI-549, the only PI3K-γ inhibitor in clinical development, offers a unique approach to enhance the anti-tumor immune response. We encapsulated IPI-549 in targeted polymeric nanoparticles (NP) and tested its activity in both murine pancreatic cancer and melanoma models. IPI-549 NP significantly decreased tumor growth and prolonged host survival in both models. Importantly, IPI-549 NP treatment reduced the suppressive tumor microenvironment by decreasing both suppressive myeloid and plasma cells in the tumor. We concluded that IPI-549 NP delivery could be a promising method for treating pancreatic cancer and other immune-suppressive tumors.

Entities: CellLine Chemical Disease Gene Mutation Species

Keywords: IPI-549; MDSC; Nanoparticle; Pancreatic cancer; Regulatory B cell

Year: 2019 PMID： 31362079 PMCID： PMC6815713 DOI： 10.1016/j.jconrel.2019.07.039

Source DB: PubMed Journal: J Control Release ISSN： 0168-3659 Impact factor: 9.776

58 in total

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Authors: Shohei Hori; Takashi Nomura; Shimon Sakaguchi
Journal: Science Date: 2003-01-09 Impact factor: 47.728

2. Hif1a Deletion Reveals Pro-Neoplastic Function of B Cells in Pancreatic Neoplasia.

Authors: Kyoung Eun Lee; Michelle Spata; Lauren J Bayne; Elizabeth L Buza; Amy C Durham; David Allman; Robert H Vonderheide; M Celeste Simon
Journal: Cancer Discov Date: 2015-12-29 Impact factor: 39.397

3. IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor.

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4. Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis.

Authors: Masanori Kobayashi; Shigetaka Shimodaira; Kazuhiro Nagai; Masahiro Ogasawara; Hidenori Takahashi; Hirofumi Abe; Mitsugu Tanii; Masato Okamoto; Sun-Ichi Tsujitani; Seiichi Yusa; Takefumi Ishidao; Junji Kishimoto; Yuta Shibamoto; Masaki Nagaya; Yoshikazu Yonemitsu
Journal: Cancer Immunol Immunother Date: 2014-04-29 Impact factor: 6.968

5. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression.

Authors: Michael C Schmid; Christie J Avraamides; Holly C Dippold; Irene Franco; Philippe Foubert; Lesley G Ellies; Lissette M Acevedo; Joan R E Manglicmot; Xiaodan Song; Wolfgang Wrasidlo; Sara L Blair; Mark H Ginsberg; David A Cheresh; Emilio Hirsch; Seth J Field; Judith A Varner
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6. Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in subjects with adenocarcinoma of the pancreas.

Authors: Marcherie Davis; Kevin Conlon; Gerald C Bohac; John Barcenas; William Leslie; LaTanja Watkins; Ihab Lamzabi; Youping Deng; Yan Li; Janet M D Plate
Journal: J Immunother Date: 2012-10 Impact factor: 4.456

7. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions.

Authors: Nobuyoshi Hiraoka; Kaoru Onozato; Tomoo Kosuge; Setsuo Hirohashi
Journal: Clin Cancer Res Date: 2006-09-15 Impact factor: 12.531

8. Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.

Authors: Barbara Morandi; Lorenzo Mortara; Laura Chiossone; Roberto S Accolla; Maria Cristina Mingari; Lorenzo Moretta; Alessandro Moretta; Guido Ferlazzo
Journal: PLoS One Date: 2012-06-19 Impact factor: 3.240

9. Murine pancreatic adenocarcinoma dampens SHIP-1 expression and alters MDSC homeostasis and function.

Authors: Shari Pilon-Thomas; Nadine Nelson; Nasreen Vohra; Maya Jerald; Laura Pendleton; Karoly Szekeres; Tomar Ghansah
Journal: PLoS One Date: 2011-11-22 Impact factor: 3.240

10. Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma.

Authors: Abasi Ene-Obong; Andrew J Clear; Jennifer Watt; Jun Wang; Rewas Fatah; John C Riches; John F Marshall; Joanne Chin-Aleong; Claude Chelala; John G Gribben; Alan G Ramsay; Hemant M Kocher
Journal: Gastroenterology Date: 2013-07-25 Impact factor: 22.682

16 in total

Inhibiting PI3 kinase-γ in both myeloid and plasma cells remodels the suppressive tumor microenvironment in desmoplastic tumors.

1. Control of regulatory T cell development by the transcription factor Foxp3.

2. Hif1a Deletion Reveals Pro-Neoplastic Function of B Cells in Pancreatic Neoplasia.

3. IL-35 promotes pancreas cancer growth through enhancement of proliferation and inhibition of apoptosis: evidence for a role as an autocrine growth factor.

4. Prognostic factors related to add-on dendritic cell vaccines on patients with inoperable pancreatic cancer receiving chemotherapy: a multicenter analysis.

5. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kγ, a single convergent point promoting tumor inflammation and progression.

6. Effect of pemetrexed on innate immune killer cells and adaptive immune T cells in subjects with adenocarcinoma of the pancreas.

7. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions.

8. Dendritic cell editing by activated natural killer cells results in a more protective cancer-specific immune response.

9. Murine pancreatic adenocarcinoma dampens SHIP-1 expression and alters MDSC homeostasis and function.

10. Activated pancreatic stellate cells sequester CD8+ T cells to reduce their infiltration of the juxtatumoral compartment of pancreatic ductal adenocarcinoma.

Review 1. Nanomedicines in B cell-targeting therapies.

2. Developing PI3K Inhibitors for Respiratory Diseases.

Review 3. Myeloid-Derived Suppressor Cells as Therapeutic Targets in Uterine Cervical and Endometrial Cancers.

Review 4. Targeting Myeloid-Derived Suppressor Cells in Ovarian Cancer.

5. Inflammation and tumor progression: signaling pathways and targeted intervention.

Review 6. The therapeutic implications of immunosuppressive tumor aerobic glycolysis.

Review 7. Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?

Review 8. Recent Advancements in Nanomedicine for 'Cold' Tumor Immunotherapy.

Review 9. Exosomal miRNAs in tumor microenvironment.

Review 10. Modulation of tumor microenvironment for immunotherapy: focus on nanomaterial-based strategies.