Exosomal PD-L1 confers chemoresistance and promotes tumorigenic properties in esophageal cancer cells via upregulating STAT3/miR-21

Wang, Haojie; Qi, Yijun; Lan, Zijun; Liu, Qiwei; Xu, Jing; Zhu, Mengxi; Yang, Tingting; Shi, Ruolin; Gao, Shegan; Liang, Guozheng

doi:10.1038/s41434-022-00331-8

Cited by 14 publications

(10 citation statements)

References 58 publications

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“…29 The scientists are very concerned about the important role of STAT3 in ESCC. [30][31][32][33] At present, there are only three studies on miR-133b and STAT3. [34][35][36] The low expression of miR-133b was negatively associated with EGFR and increased p-STAT3 levels.…”

Section: Discussionmentioning

confidence: 99%

miR-133b Promotes Esophageal Squamous Cell Carcinoma Metastasis

Huang,

Liu,

Zheng

et al. 2023

Clin Med Insights Oncol

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Background: Evaluation of biological changes at the molecular level has important clinical implications for improving the survival rate of esophageal squamous cell carcinoma (ESCC). Therefore, we plan to analyze and elucidate the expression of microRNA-133b (miR-133b), M2 pyruvate kinase (PKM2), and signal transducer and activator of transcription 3 (STAT3) in ESCC and their associated clinicopathological significance. Methods: The 72 patients with ESCC were selected as the experimental study group. Normal adjacent tissues (NAT) were matched as the control group. In this study, in situ hybridization was used to detect the expression of miR-133b in ESCC, and tissue expressions of PKM2 and STAT3 were detected by immunohistochemistry, and literature review was conducted. Results: Studies had shown that the positive expression of miR-133b in NAT was significantly higher than that in ESCC (χ2 = 9.007, P = .003). PKM2 and STAT3 in ESCC had a significantly higher positive expression levels than those of NAT (χ2 = 56.523, P = .000; χ2 = 72.939, P = .000). From correlation analysis, there was a negative correlation between miR-133b and PKM2( r = −0.515, P < .001), a negative correlation between miR-133b and STAT3( r = −0.314, P = .007), and a positive correlation between PKM2 and STAT3( r = 0.771, P < .001). Conclusions: In ESCC, our study demonstrated that downregulation of miR-133b and upregulation of PKM2 and STAT3. We predict that miR-133b may inhibit the STAT3 pathway by downregulating PKM2.

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Section: Discussionmentioning

confidence: 99%

miR-133b Promotes Esophageal Squamous Cell Carcinoma Metastasis

Huang,

Liu,

Zheng

et al. 2023

Clin Med Insights Oncol

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“…GW4869 enhances the sensitivity of human myeloid leukemia cells to doxorubicin [ 107 ]. Exosomal PD-L1 induces resistance to paclitaxel by activating the STAT3/miR-21/phosphatase and tensin homolog 1 (PTEN)/Akt axis in esophageal cancer cells [ 108 ]. GW4869 reverses the paclitaxel resistance conferred by exosomal PD-L1 [ 108 ].…”

Section: Inhibitors Targeting Exosomesmentioning

confidence: 99%

“…Exosomal PD-L1 induces resistance to paclitaxel by activating the STAT3/miR-21/phosphatase and tensin homolog 1 (PTEN)/Akt axis in esophageal cancer cells [ 108 ]. GW4869 reverses the paclitaxel resistance conferred by exosomal PD-L1 [ 108 ]. GW4869 inhibits both the release of exosomes from prostate cancer cells and M2 macrophage polarization [ 109 ].…”

Section: Inhibitors Targeting Exosomesmentioning

confidence: 99%

Exosomes: Diagnostic and Therapeutic Implications in Cancer

Shim

Jeoung

2023

Pharmaceutics

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Exosomes are a subset of extracellular vesicles produced by all cells, and they are present in various body fluids. Exosomes play crucial roles in tumor initiation/progression, immune suppression, immune surveillance, metabolic reprogramming, angiogenesis, and the polarization of macrophages. In this work, we summarize the mechanisms of exosome biogenesis and secretion. Since exosomes may be increased in the cancer cells and body fluids of cancer patients, exosomes and exosomal contents can be used as cancer diagnostic and prognostic markers. Exosomes contain proteins, lipids, and nucleic acids. These exosomal contents can be transferred into recipient cells. Therefore, this work details the roles of exosomes and exosomal contents in intercellular communications. Since exosomes mediate cellular interactions, exosomes can be targeted for developing anticancer therapy. This review summarizes current studies on the effects of exosomal inhibitors on cancer initiation and progression. Since exosomal contents can be transferred, exosomes can be modified to deliver molecular cargo such as anticancer drugs, small interfering RNAs (siRNAs), and micro RNAs (miRNAs). Thus, we also summarize recent advances in developing exosomes as drug delivery platforms. Exosomes display low toxicity, biodegradability, and efficient tissue targeting, which make them reliable delivery vehicles. We discuss the applications and challenges of exosomes as delivery vehicles in tumors, along with the clinical values of exosomes. In this review, we aim to highlight the biogenesis, functions, and diagnostic and therapeutic implications of exosomes in cancer.

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“…ExoPD‐L1 can enhance the resistance of esophageal cancer cells to paclitaxel by promoting the transcription of miRNA21 by inducing STAT3 into the nucleus. [ 50 ] Notably, exoPD‐L1, rather than other extracellular forms, might serve as a biomarker for predicting tumor progression and immune checkpoint inhibitor response. A few publications have shown that exoPD‐L1 is a marker of poor outcomes after surgery or chemotherapy and radiation in patients with gastric cancer and head and neck squamous cell carcinoma (HNSCC).…”

Section: Pd‐l1 Structure and Its Functionmentioning

confidence: 99%

Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD‐L1 in Cancer Therapy

Wang,

Zhou,

Yang

et al. 2023

Advanced Science

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Cancer immunotherapy using anti‐programmed death‐ligand 1 (PD‐L1) antibodies has been used in various clinical applications and achieved certain results. However, such limitations as autoimmunity, tumor hyperprogression, and overall low patient response rate impede its further clinical application. Mounting evidence has revealed that PD‐L1 is not only present in tumor cell membrane but also in cytoplasm, exosome, or even nucleus. Among these, the dynamic and spatial heterogeneous expression of PD‐L1 in tumors is mainly responsible for the unsatisfactory efficacy of PD‐L1 antibodies. Hence, numerous studies focus on inhibiting or degrading PD‐L1 to improve immune response, while a comprehensive understanding of the molecular mechanisms underlying spatial heterogeneity of PD‐L1 can fundamentally transform the current status of PD‐L1 antibodies in clinical development. Herein, the concept of spatial heterogeneous expression of PD‐L1 is creatively introduced, encompassing the structure and biological functions of various kinds of PD‐L1 (including mPD‐L1, cPD‐L1, nPD‐L1, and exoPD‐L1). Then an in‐depth analysis of the regulatory mechanisms and potential therapeutic targets of PD‐L1 is provided, seeking to offer a solid basis for future investigation. Moreover, the current status of agents is summarized, especially small molecular modulators development directed at these new targets, offering a novel perspective on potential PD‐L1 therapeutics strategies.

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Exosomal PD-L1 confers chemoresistance and promotes tumorigenic properties in esophageal cancer cells via upregulating STAT3/miR-21

Cited by 14 publications

References 58 publications

miR-133b Promotes Esophageal Squamous Cell Carcinoma Metastasis

miR-133b Promotes Esophageal Squamous Cell Carcinoma Metastasis

Exosomes: Diagnostic and Therapeutic Implications in Cancer

Challenges Coexist with Opportunities: Spatial Heterogeneity Expression of PD‐L1 in Cancer Therapy

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