Aryl Hydrocarbon Receptor Signaling Controls CD155 Expression on Macrophages and Mediates Tumor Immunosuppression

McKay, Zachary; Brown, Michael C.; Gromeier, Matthias

doi:10.4049/jimmunol.2000792

Cited by 19 publications

(8 citation statements)

References 46 publications

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“…18 19 A recent study has confirmed higher CD155 messenger RNA expression in TAMs. 20 Similarly, CD155 is overexpressed in CRC tissue and prevents the apoptosis of cancer cells. 21 However, the CD155 expression pattern in CRC TAMs and its role in CRC pathophysiology should still be unraveled.…”

Section: Introductionmentioning

confidence: 99%

Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer

Zhu

Liang

Lan

et al. 2022

J Immunother Cancer

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BackgroundOnco-immunogenic molecule CD155 is overexpressed in various tumor microenvironments (TME) including in colorectal cancer (CRC). Tumor-associated macrophages (TAMs) are the most abundant immune cells in CRC TME and play a vital role in CRC progression and metastasis. Most studies have focused on investigating the role of CRC cell-specific CD155 on CRC progression, while the contribution of TAMs-specific CD155 is still unknown. Here, we sought to investigate the expression pattern of CD155 in CRC TAMs and its role in tumor immunity and progression.MethodsCD155 expression patterns in CRC TAMs and macrophages in paratumor or adjacent normal tissue were analyzed in 50 patients with CRC using flow cytometry and in 141 patients with CRC using immunohistochemistry. The correlation of CD155 expression level in TAMs with M1 and M2 phenotypic transition was analyzed. The role of macrophage-specific CD155 in CRC progression and tumor immune response was investigated in vitro and in vivo. We further analyzed the effect of CRC cells on the regulation of CD155 expression in macrophages.ResultsCRC TAMs from clinical samples showed robustly higher expression of CD155 than macrophages from paratumor and adjacent normal tissues. The CD155 expression level was higher in TAMs of CRC at III/IV stages compared with the I/II stages and was negatively associated with the survival of patients with CRC. CD155+ TAMs showed an M2 phenotype and higher expression of interleukin (IL)-10 and transforming growth factor (TGF)-β. CD155+ macrophages promoted CRC cell migration, invasion, and tumor growth supporting the findings from the clinical tissue analysis. This effect was mainly regulated by TGF-β-induced STAT3 activation-mediated release of matrix metalloproteinases (MMP)2 and MMP9 in CRC cells. CD155–⁄– bone marrow transplantation in wild-type mice, as well as CD155– macrophages treatment, promoted the antitumor immune response in the mice ectopic CRC model. Additionally, CRC cells released IL-4 to trigger CD155 expression in macrophages indicating the regulatory role of CRC cells in the development of CD155+ TAMs.ConclusionsThese findings indicated that CD155+ TAMs are responsible for the M2-phenotype transition, immunosuppression, and tumor progression in CRC. The specific localization of CD155+ TAMs in CRC tissue could turn into a potential therapeutic target for CRC treatment.

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Section: Introductionmentioning

confidence: 99%

Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer

Zhu

Liang

Lan

et al. 2022

J Immunother Cancer

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“…The secretion of Interleukin (IL)‐32 was obviously downregulated by Celastrol in HCT116 cells, as well as the expression of CD155 in SW480 cells. Interestingly, some reports proved that IL‐32 (Gruber et al, 2020; Khawar et al, 2017; C. Liu et al, 2020; Ohmatsu et al, 2017; Tsai et al, 2018; Yousif et al, 2013) and CD155 (Huang et al, 2019; Jin et al, 2022; McKay et al, 2021; Noguchi et al, 2019) secreted or expressed by cancer cells were not only regulated by ERK/MAPK signaling pathway but also participated in the process of macrophage polarity regulation, which provided a potential regulatory mechanism of Celastrol on the polarization of macrophages. All these results suggested that ERK/MAPK signaling pathway and related cytokines (e.g., IL‐32) and adhesion proteins (e.g., CD155) may be strongly involved in the regulation process of macrophage polarization by Celastrol in the tumor microenvironment, which needs to be further verified in vitro and in vivo.…”

Section: Resultsmentioning

confidence: 99%

Celastrol acts as a new histone deacetylase inhibitor to inhibit colorectal cancer cell growth via regulating macrophage polarity

Wang

Chen

et al. 2022

Cell Biology International

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The tumorigenesis and progression of colorectal cancer are closely related to the tumor microenvironment, especially inflammatory response. Inhibitors of histone deacetylase (HDAC) have been reported as epigenetic regulators of the immune system to treat cancer and inflammatory diseases and our results demonstrated that Celastrol could act as a new HDAC inhibitor. Considering macrophages as important members of the tumor microenvironment, we further found that Celastrol could influence the polarization of macrophages to inhibit colorectal cancer cell growth. Specially, we used the supernatant of HCT116 and SW480 cells to induce Ana-1 cells in vitro and chose the spontaneous colorectal cancer model APC min/+ mice as an animal model to validate in vivo. The results indicated that Celastrol could reverse the polarization of macrophages from M2 to M1 through impacting the colorectal tumor microenvironment both in vitro and in vivo. Furthermore, using bioinformatics analysis, we found that Celastrol might mechanistically polarize the macrophages through MAPK signaling pathway. In conclusion, our findings identified that Celastrol as a new HDAC inhibitor and suggested that Celastrol could modulate macrophage polarization, thus inhibiting colorectal cancer growth, which may provide some novel therapeutic strategies for colorectal cancer.

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“…In glioblastoma, Kyn produced by cancer cells triggers AhR-signaling to regulate the phenotype of TAMs, and causes the production of adenosine by CD39 and CD73 in TAMs, ultimately leading to CD8 + T cells dysfunction [ 151 ]. In addition, AhR signaling mediates tumor immunosuppression by promoting CD155 expression on TAMs [ 152 ]. CD155, an immune checkpoint as a target for tumor immunotherapy, is universally expressed in solid tumors [ 153 , 154 ].…”

Section: Role Of Ido1 In Tmementioning

confidence: 99%

The Role of Indoleamine 2, 3-Dioxygenase 1 in Regulating Tumor Microenvironment

Huang

Zhang

Wang

et al. 2022

Cancers

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Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting enzyme that metabolizes an essential amino acid tryptophan (Trp) into kynurenine (Kyn), and it promotes the occurrence of immunosuppressive effects by regulating the consumption of Trp and the accumulation of Kyn in the tumor microenvironment (TME). Recent studies have shown that the main cellular components of TME interact with each other through this pathway to promote the formation of tumor immunosuppressive microenvironment. Here, we review the role of the immunosuppression mechanisms mediated by the IDO1 pathway in tumor growth. We discuss obstacles encountered in using IDO1 as a new tumor immunotherapy target, as well as the current clinical research progress.

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Aryl Hydrocarbon Receptor Signaling Controls CD155 Expression on Macrophages and Mediates Tumor Immunosuppression

Cited by 19 publications

References 46 publications

Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer

Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer

Celastrol acts as a new histone deacetylase inhibitor to inhibit colorectal cancer cell growth via regulating macrophage polarity

The Role of Indoleamine 2, 3-Dioxygenase 1 in Regulating Tumor Microenvironment

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