bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2022–10–16
fiveteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Advances in Exosomes as Diagnostic and Therapeutic Biomarkers for Gynaecological Malignancies.
  2. Effects of exosomes on tumor immunomodulation and their potential clinical applications (Review).
  3. Exosomes as diagnostic tools.
  4. Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion.
  5. Emerging Roles of Exosomes in Cancer for Possible Clinical Use.
  6. Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis.
  7. Recent Advances in Detection for Breast-Cancer-Derived Exosomes.
  8. Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo?
  9. Mesenchymal stem cell-derived exosomes as new tools for delivery of miRNAs in the treatment of cancer.
  10. Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma.
  11. Downregulation of exosomal miR-7-5p promotes breast cancer migration and invasion by targeting RYK and participating in the atypical WNT signalling pathway.
  12. Exosomal DNAJB11 promotes the development of pancreatic cancer by modulating the EGFR/MAPK pathway.
  13. The Role of Exosomes in Health and Disease.
  14. Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression.
  15. Blood exosome PD-L1 is associated with PD-L1 expression measured by immunohistochemistry, and lymph node metastasis in lung cancer.
  1. Cancers (Basel). 2022 Sep 28. pii: 4743. [Epub ahead of print]14(19):
    Advances in Exosomes as Diagnostic and Therapeutic Biomarkers for Gynaecological Malignancies.
    Mengdan Miao, Yifei Miao, Yanping Zhu, Junnan Wang, Huaijun Zhou.
       BACKGROUND: Exosomes are extracellular vesicles that can be released by practically all types of cells. They have a diameter of 30-150 nm. Exosomes control the exchange of materials and information between cells. This function is based on its special cargo-carrying and transporting functions, which can load a variety of useful components and guarantee their preservation. Recently, exosomes have been confirmed to play a significant role in the pathogenesis, diagnosis, treatment, and prognosis of gynaecological malignancies. Particularly, participation in liquid biopsy was studied extensively in gynaecological cancer, which holds the advantages of noninvasiveness and individualization.
    LITERATURE REVIEW: This article reviews the latest research progress of exosomes in gynaecological malignancies and discusses the involvement of humoral and cell-derived exosomes in the pathogenesis, progression, metastasis, drug resistance and treatment of ovarian cancer, cervical cancer, and endometrial cancer. Advances in the clinical application of exosomes in diagnostic technology, drug delivery, and overcoming tumour resistance are also presented.
    CONCLUSION: Exosomes are potentially diagnostic and prognostic biomarkers in gynaecological malignancies, and also provide new directions for the treatment of gynaecological tumours, showing great clinical potential.
    Keywords:  advances; diagnostic markers; drug delivery; exosomes; gynaecological malignancies
    DOI:  https://doi.org/10.3390/cancers14194743
  2. Int J Oncol. 2022 Dec;pii: 147. [Epub ahead of print]61(6):
    Effects of exosomes on tumor immunomodulation and their potential clinical applications (Review).
    Man Li, Hongzhen Cai, Ruiyi Deng, Jin Cheng, Yanyan Shi.
      Exosomes are small extracellular vesicles containing proteins, nucleic acids and lipids, which can transmit information between cells, and can interfere with the epigenetic characteristics and functions of recipient cells. Tumor‑derived exosomes play a crucial role as communicators in the tumor microenvironment, and are involved in the occurrence and development of various tumors. The present review article summarizes the biogenesis of exosomes and their communication with local and remote cells, focusing on the function of tumor‑derived exosomes in the tumor microenvironment, including the promotion of angiogenesis, the induction of epithelial mesenchymal transformation, and the activation and inhibition of immune cells, as well as the effects of exosomes on the tumor microenvironment during microbial infections. Additionally, the effects of exosomes on tumor immunotherapy and the potential applications of exosomes as biomarkers, delivery vehicles and cancer vaccines in cancer diagnostics and therapeutics are discussed.
    Keywords:  clinical applications; exosome; immunotherapy; tumor immunomodulation
    DOI:  https://doi.org/10.3892/ijo.2022.5437
  3. Adv Clin Chem. 2022 ;pii: S0065-2423(22)00046-4. [Epub ahead of print]110 117-144
    Exosomes as diagnostic tools.
    Shweta Gupta, P B Mazumder.
      Exosomes have evolved into novel candidates as diagnostic tools due to their composition of proteins and nucleic acids and ability to cross hypoxic regions, the systemic circulation and blood vessel barriers. Exosomes are nano-sized extracellular vesicles that contain information from their source cells and are found in almost all body fluids. In this chapter, we have focused on basic biogenesis, contents, and functions of these unique particles, and provide a comprehensive discussion on their usefulness as novel diagnostic tools in various diseases. In addition, these unique features make them potential candidates for development of advanced therapeutics and monitoring thereof.
    Keywords:  Cancer; Cardiovascular disease; Diagnostic tools; Exosomes; Neurodegenerative disease; Pregnancy disorders
    DOI:  https://doi.org/10.1016/bs.acc.2022.06.004
  4. Int J Mol Sci. 2022 Oct 04. pii: 11789. [Epub ahead of print]23(19):
    Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion.
    Xuejun Shao, Shenghao Hua, Tao Feng, Dickson Kofi Wiredu Ocansey, Lei Yin.
      Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial-mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.
    Keywords:  angiogenesis; exosome; hypoxia; immune cell; immune evasion; metastasis; surface recognition molecule; therapy resistance
    DOI:  https://doi.org/10.3390/ijms231911789
  5. Cancers (Basel). 2022 Sep 22. pii: 4603. [Epub ahead of print]14(19):
    Emerging Roles of Exosomes in Cancer for Possible Clinical Use.
    Hedwig Sutterlüty, Klaus Holzmann.
      Exosomes are membrane-structured extracellular vesicles (EVs) with nano-scale size that are released from different cell types [...].
    DOI:  https://doi.org/10.3390/cancers14194603
  6. J Exp Clin Cancer Res. 2022 Oct 10. 41(1): 296
    Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis.
    Shengkui Qiu, Li Xie, Chen Lu, Chao Gu, Yiwen Xia, Jialun Lv, Zhe Xuan, Lang Fang, Jing Yang, Lu Zhang, Zheng Li, Weizhi Wang, Hao Xu, Bowen Li, Zekuan Xu.
       BACKGROUND: Liver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but the molecular mechanism underlying gastric cancer liver metastasis (GC-LM) remains unknown. Exosomes have been identified as an important mediator of communication between tumor cells and the microenvironment. Therefore, we sought to investigate the effects of primary GC cells on the liver microenvironment and the role of exosomal microRNAs (exo-miRNA) in GC-LM.
    METHODS: Sequential differential centrifugation, transmission electron microscopy and NanoSight analysis were used to extract and characterize exosomes. MicroRNA sequencing in GC-derived exosomes and mRNA sequencing in PMA-treated THP-1 cells were used to identify differentially expressed miRNAs in exosomes and the functional targets of exosomal miR-519a-3p (exo-miR-519a-3p) in macrophages, respectively. Tracing and internalization of exosomes and transfer of exo-miR-519a-3p were observed by immunofluorescence. Tubule formation assays, aortic ring assays, and exosome-educated GC-LM model were used to investigate the roles of GC-derived exosomes and exo-miR-519a-3p in angiogenesis and GC-LM. Luciferase reporter assay, qRT-PCR, Western blot, ELISA, flow cytometry and immunofluorescence were used to investigate the regulatory mechanism of exo-miR-519a-3p at GC-LM.
    RESULTS: The expression level of miR-519a-3p in serum exosomes was significantly higher in GC-LM patients than in patients without LM, and high expression of exo-miR-519a-3p indicates a worse prognosis. GC-derived exosomes are mainly accumulated in the liver and internalized by intrahepatic macrophages. Mechanistically, exo-miR-519a-3p activates the MAPK/ERK pathway by targeting DUSP2, thereby causing M2-like polarization of macrophages. M2-like polarized macrophages accelerate GC-LM by inducing angiogenesis and promoting intrahepatic premetastatic niche formation.
    CONCLUSIONS: Our results indicate that exo-miR-519a-3p plays a critical role in mediating crosstalk between primary GC cells and intrahepatic macrophages and is a potential therapeutic target for GC-LM.
    Keywords:  Angiogenesis; Exosomes; Gastric cancer liver metastasis; M2-like polarization; miR-519a-3p
    DOI:  https://doi.org/10.1186/s13046-022-02499-8
  7. Molecules. 2022 Oct 07. pii: 6673. [Epub ahead of print]27(19):
    Recent Advances in Detection for Breast-Cancer-Derived Exosomes.
    Qin Tang, Xinying Xiao, Ranhao Li, Hailun He, Shanni Li, Changbei Ma.
      Breast cancer is the most common malignant tumor in women, its incidence is secret, and more than half of the patients are diagnosed in the middle and advanced stages, so it is necessary to develop simple and efficient detection methods for breast cancer diagnosis to improve the survival rate and quality of life of breast cancer patients. Exosomes are extracellular vesicles secreted by all kinds of living cells, and play an important role in the occurrence and development of breast cancer and the formation of the tumor microenvironment. Exosomes, as biomarkers, are an important part of breast cancer fluid biopsy and have become ideal targets for the early diagnosis, curative effect evaluation, and clinical treatment of breast cancer. In this paper, several traditional exosome detection methods, including differential centrifugation and immunoaffinity capture, were summarized, focusing on the latest research progress in breast cancer exosome detection. It was summarized from the aspects of optics, electrochemistry, electrochemiluminescence and other aspects. This review is expected to provide valuable guidance for exosome detection of clinical breast cancer and the establishment of more reliable, efficient, simple and innovative methods for exosome detection of breast cancer in the future.
    Keywords:  breast cancer; electrochemical method; exosomes; nanomaterial; optical method
    DOI:  https://doi.org/10.3390/molecules27196673
  8. Cancer Biol Ther. 2022 Dec 31. 23(1): 1-13
    Exosomal epidermal growth factor receptor is involved in HPV-16 E7-induced epithelial-mesenchymal transition of non-small cell lung cancer cells: A driver of signaling in vivo?
    Zhiyuan Zhou, Xiaofeng Wu, Riming Zhan, Xiangyong Li, Dazhao Cheng, Li Chen, Tianyu Wang, Hua Yu, Guihong Zhang, Xudong Tang.
      Our previous studies have demonstrated that human papillomavirus (HPV)-16 E7 oncoprotein promoted epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells. Moreover, recent studies have found that exosomes can mediate EMT of NSCLC cells and epidermal growth factor receptor (EGFR) is related to the progression of NSCLC. Here, we further investigated the role of exosomal EGFR in HPV-16 E7-induced EMT of NSCLC cells. Our results showed that the exosomes derived from the stable HPV-16 E7-overexpressing A549 and NCI-H460 NSCLC cells (E7 Exo) significantly increased migration, invasion, and proliferation abilities of NSCLC cells as compared with the exosomes derived from empty vector-infected NSCLC cells (ev Exo). Moreover, both in vitro and in vivo results demonstrated that E7 Exo dramatically enhanced EMT of NSCLC cells and promoted the growth of subcutaneous NSCLC xenografts. Additionally, HPV-16 E7 enhanced the expression of EGFR and p-EGFR in both NSCLC cells and exosomes. Furthermore, the inhibition of EGFR activation or exosome secretion suppressed E7 Exo-induced migration, invasion, and EMT of NSCLC. Moreover, 12 kinds of differentially expressed miRNAs between E7 Exo and ev Exo (fold change≥2, P ≤ .05) were screened out, of which 7 miRNAs were up-regulated while 5 miRNAs were down-regulated in A549 E7 Exo. Taken together, our findings suggest that exosomal EGFR is involved in HPV-16 E7-induced EMT of NSCLC cells, which may play a key role in the progression of HPV-related NSCLC.
    Keywords:  EGFR; EMT; Exosomes; HPV-16 E7; NSCLC
    DOI:  https://doi.org/10.1080/15384047.2022.2133332
  9. Front Bioeng Biotechnol. 2022 ;10 956563
    Mesenchymal stem cell-derived exosomes as new tools for delivery of miRNAs in the treatment of cancer.
    Aysegul Dalmizrak, Ozlem Dalmizrak.
      Although ongoing medical research is working to find a cure for a variety of cancers, it continues to be one of the major causes of death worldwide. Chemotherapy and immunotherapy, as well as surgical intervention and radiation therapy, are critical components of cancer treatment. Most anti-cancer drugs are given systemically and distribute not just to tumor tissues but also to normal tissues, where they may cause side effects. Furthermore, because anti-cancer drugs have a low delivery efficiency, some tumors do not respond to them. As a result, tumor-targeted drug delivery is critical for improving the safety and efficacy of anti-cancer treatment. Exosomes are microscopic extracellular vesicles that cells produce to communicate with one another. MicroRNA (miRNA), long non-coding RNA (lncRNA), small interfering RNA (siRNA), DNA, protein, and lipids are among the therapeutic cargos found in exosomes. Recently, several studies have focused on miRNAs as a potential therapeutic element for the treatment of cancer. Mesenchymal stem cells (MSC) have been known to have angiogenic, anti-apoptotic, anti-inflammatory and immunomodulatory effects. Exosomes derived from MSCs are gaining popularity as a non-cellular alternative to MSC-based therapy, as this method avoids unwanted lineage differentiation. Therefore more research have focused on transferring miRNAs to mesenchymal stem cells (MSC) and targeting miRNA-loaded exosomes to cancer cells. Here, we initially gave an overview of the characteristics and potentials of MSC as well as the use of MSC-derived exosomes in cancer therapy. Finally, we emphasized the utilization of MSC-derived exosomes for miRNA delivery in the treatment of cancer.
    Keywords:  cancer therapy; cell free therapy; exosomes; mesenchymal stem cells; micro RNA
    DOI:  https://doi.org/10.3389/fbioe.2022.956563
  10. Front Cell Dev Biol. 2022 ;10 927251
    Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma.
    Jingwen Yang, Weiwei Dong, He Zhang, Huixia Zhao, Zhiyan Zeng, Fengyun Zhang, Qiuwen Li, Xiaohong Duan, Yanyan Hu, Wenhua Xiao.
      Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC. Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC). Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%). Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.
    Keywords:  diagnostic biomarker; exosome; hepatocellular carcinoma; microRNA; plasma
    DOI:  https://doi.org/10.3389/fcell.2022.927251
  11. Cell Mol Biol Lett. 2022 Oct 09. 27(1): 88
    Downregulation of exosomal miR-7-5p promotes breast cancer migration and invasion by targeting RYK and participating in the atypical WNT signalling pathway.
    Zhaoyi Liang, Lu Liu, Ruixia Gao, Chengchuan Che, Ge Yang.
       BACKGROUND: Current studies show that exosomal miRNAs become an important factor in cancer metastasis. Among the many miRNA studies, miR-7-5p has not been thoroughly investigated in breast cancer metastasis.
    METHODS: Bioinformatic screening was performed using extant data from the GEO database, and miR-7-5p expression levels in breast cancer cell lines and exosomes were further examined using real-time quantitative PCR (qRT-PCR). The extracted exosomes were characterised by transmission electron microscopy (TEM), particle size analysis and marker protein determination. Cell migration and invasion were then examined using wound healing assays and Transwell assays, respectively. Correlation between miR-7-5p and receptor-like tyrosine kinase (RYK) was analysed by luciferase reporter. The effect of miR-7-5p against RYK-related downstream factors was verified using western blot assays.
    RESULTS: In this study, we found that the expression of miR-7-5p was significantly different in exosomes secreted from breast cancer cell lines with different high and low invasiveness. Further experiments revealed that miR-7-5p has an important role in inhibiting the migration and invasion of breast cancer. In terms of mechanism of action, miR-7-5p was found to target the RYK, leading to its reduced expression, which in turn caused a reduction in the phosphorylation level of the downstream factor JNK. Reduced levels of phosphorylated JNK factors lead to reduced levels of phosphorylation of c-Jun protein, which in turn leads to increased expression of EMT transcription factors, thereby inhibiting the epithelial-mesenchymal transition (EMT) process to suppress the invasion of breast cancer.
    CONCLUSION: Thus, we demonstrated that exosomes loaded with high levels of miR-7-5p emitted from less aggressive breast cancers can participate in the atypical WNT pathway by targeting the RYK gene and thus inhibit breast cancer metastasis.
    Keywords:  Atypical WNT pathway; Breast cancer; EMT; Exosome; RYK; miR-7-5p
    DOI:  https://doi.org/10.1186/s11658-022-00393-x
  12. Cell Mol Biol Lett. 2022 Oct 08. 27(1): 87
    Exosomal DNAJB11 promotes the development of pancreatic cancer by modulating the EGFR/MAPK pathway.
    Peng Liu, Fuqiang Zu, Hui Chen, Xiaoli Yin, Xiaodong Tan.
      Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with invasive and metastatic characteristics and poor prognosis. Intracellular protein homeostasis is associated with invasion and metastasis of pancreatic cancer, but the specific molecular mechanism remains unclear. Our previous studies have revealed that DNAJB11, a key protein in protein homeostasis, is secreted by exosomes in the supernatant of dissociated pancreatic cancer cells with high metastasis. The results from transcriptome sequencing and co-immunoprecipitation (Co-IP)-based liquid chromatography with tandem mass spectrometry (LC-MS/MS) showed that depletion of DNAJB11 levels could increase HSPA5 expression and induce endoplasmic reticulum stress through the PRKR-like endoplasmic reticulum kinase signaling pathway in pancreatic cancer cells. Furthermore, exosomal DNAJB11 promoted cell development of PC cells in vitro and in vivo. In addition, exosomal DNAJB11 could regulate the expression of EGFR and activate the downstream MAPK signaling pathway. Clinical blood samples were collected to evaluate the potential of exosome DNAJB11 as a diagnostic biomarker and therapeutic target for the treatment of pancreatic cancer. This study could provide a new theoretical basis and potential molecular targets for the treatment of pancreatic cancer.
    Keywords:  Early diagnosis; Exosomal protein; Pancreatic cancer; Signal transduction
    DOI:  https://doi.org/10.1186/s11658-022-00390-0
  13. Int J Mol Sci. 2022 Sep 20. pii: 11011. [Epub ahead of print]23(19):
    The Role of Exosomes in Health and Disease.
    Vincenzo Lionetti.
      Who would have thought that the discovery made by researchers at Washington University [...].
    DOI:  https://doi.org/10.3390/ijms231911011
  14. Cancers (Basel). 2022 Sep 23. pii: 4612. [Epub ahead of print]14(19):
    Pancreatic Cancer Cell-Derived Exosomes Promote Lymphangiogenesis by Downregulating ABHD11-AS1 Expression.
    Xulin Zhou, Fengyun Zhong, Yongmin Yan, Sihui Wu, Huizhi Wang, Junqiang Liu, Feifan Li, Dawei Cui, Min Xu.
      Research on pancreatic cancer microbiomes has attracted attention in recent years. The current view is that enriched microbial communities in pancreatic cancer tissues may affect pancreatic cancer metastasis, including lymph node (LN) metastasis. Similar to carriers of genetic information between cells, such as DNA, mRNA, protein, and non-coding RNA, exosomes are of great importance in early LN metastasis in tumors, including pancreatic cancer. Our previous study showed that the long non-coding RNA ABHD11-AS1 was highly expressed in tissues of patients with pancreatic cancer, and was correlated with patient survival time. However, the role of ABHD11-AS1 in pancreatic cancer LN metastasis has rarely been studied. Hence, in this paper we confirmed that exosomes derived from pancreatic cancer cells could promote lymphangiogenesis in vitro and in vivo, and that the mechanism was related to the downregulation of ABHD11-AS1 expression in lymphatic endothelial cells, and to the enhancement of their ability to proliferate, migrate, and form tubes. These findings preliminarily show a new mechanism by which pancreatic cancer cells regulate peripheral lymphangiogenesis, providing a new therapeutic strategy for inhibiting LN metastasis in pancreatic cancer.
    Keywords:  ABHD11-AS1; exosomes; lymphangiogenesis; pancreatic cancer
    DOI:  https://doi.org/10.3390/cancers14194612
  15. Tissue Cell. 2022 Sep 17. pii: S0040-8166(22)00213-0. [Epub ahead of print]79 101941
    Blood exosome PD-L1 is associated with PD-L1 expression measured by immunohistochemistry, and lymph node metastasis in lung cancer.
    Zhen Zhang, Weizhong Jin, Kai Xu, Xiaofang Zheng, You Zhou, Man Luo, Chenhong Yan, Xiuxiu Zheng, Er Jin.
       BACKGROUND: Previous observations illustrated that programmed cell death ligand 1 in exosomes (Exo-PD-L1) may lead to immunosuppression. This study proposed to investigate the significance of Exo-PD-L1 and the results of PD-L1 immunohistochemistry (IHC) assay in the clinical diagnosis and treatment of lung cancer.
    METHODS: 29 lung cancer patients were enrolled. Exosomes were extracted from the blood of patients and purified, and the extracts were identified by Western blot and transmission electron microscope. Next, the levels of Exo-PD-L1 and PD-L1 in tumor tissue were evaluated by enzyme-linked immunosorbent assay (ELISA) and IHC, respectively. The correlation between Exo-PD-L1, IHC PD-L1 status and pathological features of patients was analyzed by applying Chi-square test. After immune checkpoint inhibitor (ICI) treatment, the objective response rate (ORR) was calculated, and drug response prediction in lung cancer patients by using Exo-PD-L1 alone, IHC PD-L1 alone, and their combined detection were analyzed.
    RESULTS: This study confirmed that lung cancer patients had much expression of PD-L1 in blood exosomes and that Exo-PD-L1 level was associated with IHC PD-L1 status. The expression level of Exo-PD-L1 was evidently related to the positive lymph node metastasis of lung cancer patients, while IHC PD-L1 status was not correlated with clinicopathological features of patients. Moreover, Exo-PD-L1 and IHC PD-L1 alone or their combined detection could be utilized to predict the efficacy of ICI therapy in lung cancer patients.
    CONCLUSION: The correlation between Exo-PD-L1 and IHC PD-L1 status was indicated, and Exo-PD-L1 could assist in determining the suitable lung cancer patients suitable for ICI therapy using IHC PD-L1. This study provides references for the application of Exo-PD-L1 as an effective predictor of ICI therapy.
    Keywords:  Exo-PD-L1; ICI therapy; IHC PD-L1; Lung cancer
    DOI:  https://doi.org/10.1016/j.tice.2022.101941
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