PD-L1 promotes myofibroblastic activation of hepatic stellate cells by distinct mechanisms selective for TGF-β receptor I versus II

Sun, Liankang; Wang, Yuanguo; Wang, Xianghu; Navarro‐Corcuera, Amaia; Ilyas, Sumera; Jalan‐Sakrikar, Nidhi; Chai, Guoqiang; Tu, Xinyi; Shi, Yu; Tu, Kangsheng; Liu, Qingguang; Lou, Zhenkun; Dong, Haidong; Sharpe, Arlene H.; Shah, Vijay H.; Kang, Ningling

doi:10.1016/j.celrep.2022.110349

Cited by 23 publications

(22 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the MCF7 cell line, the mRNA of both cytokines was measured at comparable levels, whereas TNFα was produced 3-to-8-times more than TGFβ in the T47D cells (not shown). Consistent with its role in myofibroblast transition [ 39 , 40 ], we also measured CD274 (PD-L1) expression in both populations. CD274 was hardly, if at all, detectable in control cells, indicating that its expression was dependent on a paracrine stimulus ( Figure 4 B–D).…”

Section: Resultssupporting

confidence: 54%

“…These observations underscore the existence of CD274 (PD-L1) effects that are independent of PD-L1/PD1 binding. Furthermore, in intrahepatic cholangiocarcinoma (ICC), myofibroblastic CD274 plays a crucial role in modulating both the tumor microenvironment and tumor growth, independent of immune suppression function [ 40 ]. Targeting CD274 in hepatic stellate cells prevents these cells from acquiring a myofibroblastic phenotype and results in a dramatic decrease in ICC growth.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

et al. 2022

View full text Add to dashboard Cite

Breast adipose tissue (AT) participates in the physiological evolution and remodeling of the mammary gland due to its high plasticity. It is also a favorable microenvironment for breast cancer progression. However, information on the properties of human breast adipose progenitor cells (APCs) involved in breast physiology or pathology is scant. We performed differential enzymatic dissociation of human breast AT lobules. We isolated and characterized two populations of APCs. Here we report that these distinct breast APC populations selectively expressed markers suitable for characterization. The population preferentially expressing ALPL (MSCA1) showed higher adipogenic potential. The population expressing higher levels of INHBA and CD142 acquired myofibroblast characteristics upon TGF-β treatment and a myo-cancer-associated fibroblast profile in the presence of breast cancer cells. This population expressed the immune checkpoint CD274 (PD-L1) and facilitated the expansion of breast cancer mammospheres compared with the adipogenic population. Indeed, the breast, as with other fat depots, contains distinct types of APCs with differences in their ability to specialize. This indicates that they were differentially involved in breast remodeling. Their interactions with breast cancer cells revealed differences in the potential for tumor dissemination and estrogen receptor expression, and these differences might be relevant to improve therapies targeting the tumor microenvironment.

show abstract

Section: Resultssupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

et al. 2022

View full text Add to dashboard Cite

show abstract

“…PD-L1 is required for HSC activation by stabilizing TGF-β receptors [ 74 ]. Targeting HSC PD-L1 in mice suppressed HSC activation and growth of intrahepatic cholangiocarcinoma [ 74 ].…”

Section: Activation and Deactivation Of Hscs As A Results Of Therapymentioning

confidence: 99%

Activated Hepatic Stellate Cells in Hepatocellular Carcinoma: Their Role as a Potential Target for Future Therapies

Ali

Trailin

Ambrożkiewicz

et al. 2022

IJMS

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a global healthcare challenge, which affects more than 815,000 new cases every year. Activated hepatic stellate cells (aHSCs) remain the principal cells that drive HCC onset and growth. aHSCs suppress the anti-tumor immune response through interaction with different immune cells. They also increase the deposition of the extracellular matrix proteins, challenging the reversion of fibrosis and increasing HCC growth and metastasis. Therapy for HCC was reported to activate HSCs, which could explain the low efficacy of current treatments. Conversely, recent studies aimed at the deactivation of HSCs show that they have been able to inhibit HCC growth. In this review article, we discuss the role of aHSCs in HCC pathophysiology and therapy. Finally, we provide suggestions for the experimental implementation of HSCs in HCC therapies.

show abstract

“…Programmed cell death ligand 1 (PD-L1) as a known immune checkpoint molecule could induce immune tolerance in the TME, however, a recent study found that PDL1 expressed by HSCs was required for the transformation of HSCs into myofibroblasts but was independent of the immunosuppressive function of PDL1. Mechanistically, the PD-L1 extracellular domain bound to TGF-β receptors II (TβRII) of HSCs to protect TβRII from lysosomal degradation, and the cytoplasmic domain of PD-L1 protected TGF-β receptors I (TβRI) mRNA from degradation by the RNA exosome complex in HSCs [ 169 ].…”

Section: The Roles Of Cafs In Cca Progressionmentioning

confidence: 99%

Advances of cancer-associated fibroblasts in liver cancer

2022

View full text Add to dashboard Cite

Liver cancer is one of the most common malignant tumors worldwide, it is ranked sixth in incidence and fourth in mortality. According to the distinct origin of malignant tumor cells, liver cancer is mainly divided into hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Since most cases are diagnosed at an advanced stage, the prognosis of liver cancer is poor. Tumor growth depends on the dynamic interaction of various cellular components in the tumor microenvironment (TME). As the most abundant components of tumor stroma, cancer-associated fibroblasts (CAFs) have been involved in the progression of liver cancer. The interplay between CAFs and tumor cells, immune cells, or vascular endothelial cells in the TME through direct cell-to-cell contact or indirect paracrine interaction, affects the initiation and development of tumors. Additionally, CAFs are not a homogeneous cell population in liver cancer. Recently, single-cell sequencing technology has been used to help better understand the diversity of CAFs in liver cancer. In this review, we mainly update the knowledge of CAFs both in HCC and CCA, including their cell origins, chemoresistance, tumor stemness induction, tumor immune microenvironment formation, and the role of tumor cells on CAFs. Understanding the context-dependent role of different CAFs subsets provides new strategies for precise liver cancer treatment.

show abstract

PD-L1 promotes myofibroblastic activation of hepatic stellate cells by distinct mechanisms selective for TGF-β receptor I versus II

Cited by 23 publications

References 50 publications

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

Identification of Human Breast Adipose Tissue Progenitors Displaying Distinct Differentiation Potentials and Interactions with Cancer Cells

Activated Hepatic Stellate Cells in Hepatocellular Carcinoma: Their Role as a Potential Target for Future Therapies

Advances of cancer-associated fibroblasts in liver cancer

Contact Info

Product

Resources

About