Macrophage polarization as a novel weapon in conditioning tumor microenvironment for bladder cancer: can we turn demons into gods?

Rubio, Carolina; Munera-Maravilla, Ester; Lodewijk, Iris; Suárez-Cabrera, Cristian; Karaivanova, V.; Ruiz-Palomares, Raquel; Paramio, Jesús M.; Dueñas, Marta

doi:10.1007/s12094-018-1952-y

Cited by 34 publications

(27 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In NMIBC these TAMs are induced and maintained by Bone Morphogenetic Protein 4 (BMP4) secreted by the tumor cells (12). They are able to suppress adaptive immunity, support tumor growth and angiogenesis and aid cell migration, invasion and metastasis (13).…”

Section: The Gold Standard Immunomodulatory Approach To Treat Nmibc: mentioning

confidence: 99%

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

2020

View full text Add to dashboard Cite

It is now well-recognized that the tumor microenvironment (TME) is not only a key regulator of cancer progression but also plays a crucial role in cancer treatment responses. Recently, several high-profile publications have demonstrated the importance of particular immune parameters and cell types that dictate responsiveness to immunotherapies. With this increased understanding of TME-mediated therapy, approaches that increase therapeutic efficacy by remodeling the TME are actively being pursued. A classic example of this, in practice by urologists for over 40 years, is the manipulation of the bladder microenvironment for the treatment of non-muscle invasive bladder cancer (NMIBC) by instillation of intravesical bacillus Calmette-Guerin (BCG). The success of BCG treatment is thought to be due to its ability to induce a massive influx of Th1-polarized inflammatory cells, production of Th1 inflammatory cytokines and the generation of tumor-targeted Th1-mediated cytotoxic responses. Whilst BCG immunotherapy is currently the best treatment for NMIBC, ∼30% of patients show no response to this treatment. Here we present a review highlighting a variety of promising alternative immunotherapies being developed that remodel the bladder tumor microenvironment. These include (1) the use of oncolytic viruses which selectively replicate within cancer cells whilst also modifying the immunological components of the TME, (2) manipulation of the bladder microbiome to augment the response to BCG or other immunotherapies (3) utilizing Toll-like Receptor agonists as anti-tumor agents due to their potent stimulation of innate and adaptive immunity and (4) the growing recognition that immunotherapeutic strategies that will have the largest impact on patients may require multiple therapeutic approaches combined together. The accumulating knowledge on TME remodeling holds promise for providing an alternative therapy for patients with BCG-unresponsive NMIBC.

show abstract

Section: The Gold Standard Immunomodulatory Approach To Treat Nmibc: mentioning

confidence: 99%

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

2020

View full text Add to dashboard Cite

show abstract

“…In human bladder cancer, increased infiltration of tumor associated macrophages has been showed to be associated with the poor clinical prognosis [27]. Some researcher suggested that targeting macrophage may be a promising strategy for anticancer therapy [28,29]. Our analyses revealed t a high level of macrophages M0 and M1 existed in BLCA.…”

Section: Discussionmentioning

confidence: 61%

Immune Cell Infiltration in Bladder Cancer

Liu

et al. 2019

Preprint

View full text Add to dashboard Cite

Background Bladder cancer is one of the most common malignant diseases with high recurrence rates worldwide. Although immunotherapy has been applied in bladder cancer for a long period of time, the tumor-infiltrating immune cells (TIICs) in bladder cancer has not been systematical investigated. Methods CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs), was applied to calculate the TIICs fraction proportion in normal bladder tissues and in bladder cancer tissues with the TCGA data. Results compared to normal bladder tissue, B cells naïve, T cells CD4 memory resting and Mast cells resting fractions proportion decreased, and NK resting, macrophages M0 and macrophages M1 increased. In BLCAs tissue, pro-tumorigenic related immune cells were negatively correlated with anti-tumor immune cells. New tumor with locoregional had high fraction proportion of macrophages M0 and macrophages M1. Dendritic cells activated, Monocytes, macrophages M1, Tregs and T cells follicular helper significantly increased in low grade BLCAs. Tregs had a high proportion in BLCAs patients accepted low radiation dose. Conclusions This study indicates that macrophages M2 and Tregs could be the promising immunotherapy targets combined radiotherapy in BLCAs. The result provides valuable information to understand the immunity status in BLCAs.

show abstract

“…Anti-in ammatory type-2 (M2 macrophage) can promote the tumorigenesis, development, metastasis, and drug resistance of solid tumors, including bladder cancer [4][5][6], while pro-in ammatory type-1 (M1 macrophage) in turn inhibits these effects [7][8][9]. Increasing the proportion of M1-subtype cells in TME is a promising strategy for cancer treatment [10,11]. However, the role of M1-like macrophages polarized by plant polysaccharides in bladder cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Polyporus polysaccharide regulates proliferation, apoptosis and migration of bladder cancer cells by polarizing macrophages to M1 subtype in tumor microenvironment

Jia¹,

Luo²,

Lai³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Polyporus polysaccharide (PPS), an active ingredient of traditional Chinese medicinal Polyporus umbellatus, has multiple biological functions, such as anti-cancer, immune-regulating and hepatoprotective activities. The purpose of this study was to investigate the mechanism of PPS activated macrophages in the treatment of bladder cancer.Methods: 100 ng/mL Phorbol myristate acetate (PMA) was used to induce THP-1 human leukemic cells as a macrophage model. Flow cytometry was used to detect the expression of CD14 and CD68 to verify the establishment of macrophage model. After that, Macrophages derived from THP-1 were treated with different concentrations of PPS (1,10 and 100 ug/mL). Flow cytometry and RT-PCR were used to detected the expression of CD16, CD23, CD86, CD40 and interleukin (IL)-Iβ, iNOS mRNA. ELISA was used to test the change of IL-1β and TNF-α in macrophage after the treatment with PPS. The conditioned medium from PPS-polarized macrophages was used to detect the effect of activated macrophages on bladder cancer. MTT assay, 5-ethynyl-2¢-deoxyuridine assay, flow cytometry, Transwell assay, and Western blot analysis were used to detect the effects of polarized macrophages on the viability, proliferation, apoptosis, and migration of bladder cancer cells. Western blot was also used to analysis the change of JAK2/NF-κB pathway protein.Results: PPS promoted the expression of pro-inflammatory factors, such as IL-Iβ, TNF-α and iNOS, and surface molecules CD86, CD16, CD23, and CD40 in macrophages and then polarized macrophages to M1 type. The results demonstrated that activated macrophages inhibited the proliferation of bladder cancer cells, regulated their apoptosis, and inhibited migration and epithelial–mesenchymal transformation (EMT). JAK2/NF-κB pathways were downregulated in the anti-bladder cancer process of activated macrophages. Conclusion: The findings indicated that PPS inhibited the proliferation and progression of bladder cancer by the polarization of macrophages to M1 type, and JAK2/NF-κB pathway was downregulated in the process of anti-bladder cancer.

show abstract

Macrophage polarization as a novel weapon in conditioning tumor microenvironment for bladder cancer: can we turn demons into gods?

Cited by 34 publications

References 96 publications

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

Immune Cell Infiltration in Bladder Cancer

Polyporus polysaccharide regulates proliferation, apoptosis and migration of bladder cancer cells by polarizing macrophages to M1 subtype in tumor microenvironment

Contact Info

Product

Resources

About