Next Article in Journal
Functional Expression of Choline Transporters in the Blood–Brain Barrier
Next Article in Special Issue
Sarcopoterium spinosum Inhibited the Development of Non-Alcoholic Steatosis and Steatohepatitis in Mice
Previous Article in Journal
Comprehensive Detection of Isopeptides between Human Tissue Transglutaminase and Gluten Peptides
Previous Article in Special Issue
Association of Lifelong Intake of Barley Diet with Healthy Aging: Changes in Physical and Cognitive Functions and Intestinal Microbiome in Senescence-Accelerated Mouse-Prone 8 (SAMP8)
Open AccessArticle

Astragalus polysaccharides (PG2) Enhances the M1 Polarization of Macrophages, Functional Maturation of Dendritic Cells, and T Cell-Mediated Anticancer Immune Responses in Patients with Lung Cancer

1
Division of Hematology & Oncology, Department of Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
2
Department of Medical Research and Education, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
3
Division of Thoracic Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
4
Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan
5
Department of Dermatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
6
School of Medicine, Buddhist Tzu Chi University, Hualien City 970, Taiwan
7
Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan
8
Division of Thoracic Surgery, Department of Surgery, MacKay Memorial Hospital, Taipei City 104, Taiwan
9
The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei City 110, Taiwan
10
Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
11
Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan
12
Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
13
Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu City 30015, Taiwan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2019, 11(10), 2264; https://doi.org/10.3390/nu11102264
Received: 28 August 2019 / Revised: 11 September 2019 / Accepted: 17 September 2019 / Published: 20 September 2019
(This article belongs to the Special Issue Natural and Dietary Agents for Human Diseases Prevention)
Background: Recently, we demonstrated that Astragalus polysaccharide (PG2), the active ingredient in dried roots of astragalus membranaceus, ameliorates cancer symptom clusters and improves quality of life (QoL) in patients with metastatic disease by modulating inflammatory cascade against the background roles of inflammatory cells, including macrophages, dendritic cells (DCs), and cytotoxic T lymphocytes (CTLs) in tumor initiation, metastasis, and progression. Nevertheless, the role of PG2 in the modulation of anticancer immunogenicity and therapeutic response remains relatively underexplored and unclear. Purpose: The present study investigates how and to what extent PG2 modulates cellular and biochemical components of the inflammatory cascade and enhances anticancer immunity, as well as the therapeutic implication of these bio-events in patients with lung cancer. Methods and Results: Herein, we demonstrated that PG2 significantly increased the M1/M2 macrophage polarization ratio in non-small cell carcinoma (NSCLC) H441 and H1299 cells. This PG2-induced preferential pharmacologic up-regulation of tumoral M1 population in vitro positively correlated with the downregulation of tumor-promoting IL-6 and IL-10 expression in NSCLC cell-conditioned medium, with concomitant marked inhibition of cell proliferation, clonogenicity, and tumorsphere formation. Our ex vivo results, using clinical sample from our NSCLC cohort, demonstrated that PG2 also promoted the functional maturation of DCs with consequent enhancement of T cell-mediated anticancer immune responses. Consistent with the in vitro and ex vivo results, our in vivo studies showed that treatment with PG2 elicited significant time-dependent depletion of the tumor-associated M2 population, synergistically enhanced the anti-M2-based anticancer effect of cisplatin, and inhibited xenograft tumor growth in the NSCLC mice models. Moreover, in the presence of PG2, cisplatin-associated dyscrasia and weight-loss was markedly suppressed. Conclusion: These results do indicate a therapeutically-relevant role for PG2 in modulating the M1/M2 macrophage pool, facilitating DC maturation and synergistically enhancing the anticancer effect of conventional chemotherapeutic agent, cisplatin, thus laying the foundation for further exploration of the curative relevance of PG2 as surrogate immunotherapy and/or clinical feasibility of its use for maintenance therapy in patients with lung cancer. View Full-Text
Keywords: Astragalus polysaccharide; PG2; cisplatin; macrophages; monocytes; M1/M2 polarization; immunotherapy; maintenance therapy; lung cancer; NSCLC Astragalus polysaccharide; PG2; cisplatin; macrophages; monocytes; M1/M2 polarization; immunotherapy; maintenance therapy; lung cancer; NSCLC
Show Figures

Graphical abstract

MDPI and ACS Style

Bamodu, O.A.; Kuo, K.-T.; Wang, C.-H.; Huang, W.-C.; Wu, A.T.; Tsai, J.-T.; Lee, K.-Y.; Yeh, C.-T.; Wang, L.-S. Astragalus polysaccharides (PG2) Enhances the M1 Polarization of Macrophages, Functional Maturation of Dendritic Cells, and T Cell-Mediated Anticancer Immune Responses in Patients with Lung Cancer. Nutrients 2019, 11, 2264.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop