Article
Immunology
Jiming Chen, Jie Yang, Wenhui Wang, Danfeng Guo, Chengyan Zhang, Shibo Wang, Xinliang Lu, Xiaofang Huang, Pingli Wang, Gensheng Zhang, Jing Zhang, Jianli Wang, Zhijian Cai
Summary: PD-L1(+) tumor-derived extracellular vesicles (TEVs) cause resistance to anti-PD-L1 antibody therapy by decoying the antibody and being cleared by macrophages, resulting in insufficient blockade of tumor PD-L1.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Oncology
Di Xu, Wen-Quan Chen, Ming-Xing Liang, Xiu Chen, Zhen Liu, Yin-Jiao Fei, Xin-Yi Shao, Yang Wu, Wei Zhang, Jin-Hai Tang
Summary: In this study, it was discovered that BC-derived sEVs induce breast cancer metastasis through the miR-106b-5p/PTEN/AKT/PD-L1 and miR-18a-5p/PIAS3/STAT3/PD-L1 pathways in TAMs, providing promising signaling pathway inhibition strategies for the treatment of breast cancer.
CANCER CELL INTERNATIONAL
(2023)
Article
Chemistry, Multidisciplinary
Yuan Yin, Bingxin Liu, Yulin Cao, Surui Yao, Yuhang Liu, Guoying Jin, Yan Qin, Ying Chen, Kaisa Cui, Leyuan Zhou, Zehua Bian, Bojian Fei, Shenglin Huang, Zhaohui Huang
Summary: This study reveals that colorectal cancer cells can induce macrophage polarization and PD-L1 expression through the release of small extracellular vesicles (sEVs), leading to suppressed CD8(+) T cell activity and increased tumor growth. The miR-21-5p and miR-200a derived from sEVs play key regulatory roles in this process. Inhibiting the secretion of specific sEV-miRNAs from CRC and targeting PD-L1 in TAMs may serve as novel methods for CRC treatment.
Article
Chemistry, Multidisciplinary
Junli Zhang, Yifan Zhu, Mengting Guan, Yingying Liu, Min Lv, Chongwei Zhang, Hongling Zhang, Zhenzhong Zhang
Summary: Exosomes have potential as cancer biomarkers in clinical applications, but enrichment and detection from complex media remain challenging. This study used iodixanol density gradient centrifugation for exosome isolation and purification, and surface plasmon resonance (SPR) biochip for label-free detection of exosomal PD-L1. The method showed better specificity in distinguishing exosomes with different levels of PD-L1 compared to enzyme-linked immunosorbent assays.
Article
Oncology
Ihor Arkhypov, Feyza Gul Ozbay Kurt, Rebekka Bitsch, Daniel Novak, Vera Petrova, Samantha Lasser, Thomas Hielscher, Christopher Groth, Alisa Lepper, Xiaoying Hu, Wei Li, Jochen Utikal, Peter Altevogt, Viktor Umansky
Summary: Soluble HSP90 alpha can convert monocytes into MDSC, which inhibits the antitumor function of T and NK cells. Higher levels of HSP90 alpha in plasma of patients with melanoma are associated with increased PD-L1 expression on MDSC and shorter PFS after ICI therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Surbhi Mishra, Sajeen Bahadur Amatya, Sonja Salmi, Vesa Koivukangas, Peeter Karihtala, Justus Reunanen
Summary: Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have shown promise as contemporary treatments for cancer. This review discusses the potential role of microbiota-derived extracellular vesicles in improving anti-PD-1/PD-L1 therapy outcomes. Bacterial extracellular vesicles have the ability to cross barriers and modify the tumor microenvironment, offering new therapeutic avenues for cancer treatment.
Article
Chemistry, Physical
Yinzhu Lu, Bingqian Lin, Weizhi Liu, Jialu Zhang, Lin Zhu, Chaoyong Yang, Yanling Song
Summary: A modular platform is developed for sequential isolation of tumor and non-tumor extracellular vesicles (EVs) using dual-aptamer recognition and tandem microchips. This method provides new clues for assessing immune heterogeneity and can be used for EV proteome profiling.
Article
Biochemistry & Molecular Biology
Yufan Qiu, Yi Yang, Riyao Yang, Chunxiao Liu, Jung-Mao Hsu, Zhou Jiang, Linlin Sun, Yongkun Wei, Chia-Wei Li, Dihua Yu, Jin Zhang, Mien-Chie Hung
Summary: The study reveals that PD-1 can be secreted in an exosomal form by activated T cells and interact remotely with PD-L1. This interaction can attenuate the suppression of tumor-specific cytotoxic T cell activity by PD-L1, restoring tumor surveillance.
Article
Chemistry, Analytical
Jie Hao, Junyi Wang, Yan Dong, Jingyao Yang, Zhe Wang, Xiaoxin Zhao, Tian Zeng, Xiang Zhao, Houjie Liang, Jianjun Li
Summary: Breakthroughs in immune checkpoint inhibitor (ICI) therapy have revolutionized clinical tumor therapy. Monitoring exosomal PD-L1 levels provides a potential and effective liquid biopsy method for tumor immunotherapy.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Simona Serrati, Michele Guida, Roberta Di Fonte, Simona De Summa, Sabino Strippoli, Rosa Maria Iacobazzi, Alessandra Quarta, Ivana De Risi, Gabriella Guida, Angelo Paradiso, Letizia Porcelli, Amalia Azzariti
Summary: This study identified circulating PD1(+) EVs as a driver of resistance to anti-PD1 therapy in metastatic melanoma patients. The analysis of single EV populations by liquid biopsy is a promising tool for stratifying patients for immunotherapy.
Article
Biochemistry & Molecular Biology
Marzia Pucci, Stefania Raimondo, Ornella Urzi, Marta Moschetti, Maria Antonietta Di Bella, Alice Conigliaro, Nadia Caccamo, Marco Pio La Manna, Simona Fontana, Riccardo Alessandro
Summary: Tumor-derived small extracellular vesicles (SEVs) from colon cancer and multiple myeloma cells can significantly upregulate the expressions of PD-L1 and IL-6, activate the STAT3 signaling pathway, and contribute to the formation of an immunosuppressive microenvironment. The TLR4/NF-kB pathway is identified as a convergent mechanism for SEV-mediated PD-L1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Min Liu, Feng Wei, Jian Wang, Wenwen Yu, Meng Shen, Ting Liu, Dong Zhang, Yang Wang, Xiubao Ren, Qian Sun
Summary: MDSCs activate the PI3K/AKT/NF-kappa B pathway in B cells via the PD-1/PD-L1 axis, regulating the immunosuppressive function of Bregs. Inhibition of PD-1/PD-L1 or PI3K/AKT signaling suppresses tumor growth and the immunosuppressive functions of Bregs. Dual suppression of PD-1/PD-L1 and PI3K/AKT shows better antitumor effect.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Marzia Del Re, Ron Hn van Schaik, Stefano Fogli, Ron Hj Mathijssen, Federico Cucchiara, Annalisa Capuano, Cristina Scavone, Guido W. Jenster, Romano Danesi
Summary: Monoclonal antibodies targeting the PD-1/PD-L1 axis enhance immune response to cancer, but some patients do not benefit from treatment due to resistance or adverse reactions. Currently, PD-L1 expression in tumor tissues is used to predict drug response, but researchers are interested in identifying blood-based biomarkers for dynamic monitoring of response.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Review
Cell Biology
Jiaxing Liu, Xueqiang Peng, Shuo Yang, Xinyu Li, Mingyao Huang, Shibo Wei, Sheng Zhang, Guangpeng He, Hongyu Zheng, Qing Fan, Liang Yang, Hangyu Li
Summary: PD-L1 is a ligand for PD-1 and is associated with immunosuppression. PD-L1 is not only found on the surface of tumor cells, but also on the surface of extracellular vesicles secreted by these cells. Interaction between extracellular vesicle PD-L1 and PD-1 on T cells leads to immunosuppression. Exploring the production, regulation, tumor immunosuppression, and clinical application of extracellular vesicle PD-L1 is of great importance.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Microbiology
Sharda Kumari, Bhaswati Bandyopadhyay, Anamika Singh, Suruchi Aggarwal, Amit Kumar Yadav, Naval Kishore Vikram, Prasenjit Guchhait, Arup Banerjee
Summary: Extracellular vesicles (EVs) derived from plasma of severe dengue patients have immunosuppressive properties on CD4+ T cells, which may contribute to T cell suppression and dengue disease progression.
Review
Oncology
Fabian Freitag, Marius Maucher, Zeno Riester, Michael Hudecek
CURRENT OPINION IN ONCOLOGY
(2020)
Review
Oncology
Peter Altevogt, Marei Sammar, Laura Hueser, Glen Kristiansen
Summary: CD24 is a highly glycosylated protein expressed primarily by immune cells and often overexpressed in human tumors. It plays a role in regulating cell migration, invasion and proliferation in cancer, associated with poor prognosis and used as a cancer stemness marker. The review summarizes recent progress on the role of CD24-Siglec-10 binding axis in tumor immunity and the potential of CD24-based immunotherapy in cancer.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Pathology
Yuri Tolkach, Romina Zarbl, Simone Bauer, Manuel Ritter, Joerg Ellinger, Stephan Hauser, Laura Hueser, Sabine M. Klauck, Peter Altevogt, Holger Sultmann, Dimo Dietrich, Glen Kristiansen
Summary: CD24 is overexpressed in many human cancers, including prostate cancer, and its up-regulation can be influenced by DNA methylation of the CD24 promoter. Higher levels of CD24 expression are associated with poorer outcomes in prostate cancer patients, including shorter biochemical recurrence-free survival. Overexpression of ERG and PTEN deficiency are also correlated with increased CD24 expression levels in prostate cancer.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Review
Cell Biology
Rebekka Weber, Christopher Groth, Samantha Lasser, Ihor Arkhypov, Vera Petrova, Peter Altevogt, Jochen Utikal, Viktor Umansky
Summary: MDSC are crucial cells generated during tumor progression that suppress the anti-tumor functions of T and NK cells. IL-6 plays a key role in regulating the accumulation and activation of MDSC, as well as stimulating tumor cell proliferation and survival. This cytokine has pleiotropic effects on immune cell populations involved in tumor development and is a potential target for tumor immunotherapy to block MDSC-mediated immunosuppression in cancer patients.
CELLULAR IMMUNOLOGY
(2021)
Article
Cell Biology
Christoffer Gebhardt, Sonja C. S. Simon, Rebekka Weber, Mirko Gries, Dong Hun Mun, Raphael Reinhard, Tim Holland-Letz, Viktor Umansky, Jochen Utikal
Summary: Low-dose paclitaxel treatment may improve clinical outcomes for some advanced melanoma patients by enhancing antitumor immunity, potentially suggesting its use in combined melanoma immunotherapy.
CELLULAR IMMUNOLOGY
(2021)
Article
Oncology
Christopher Groth, Ludovica Arpinati, Merav E. Shaul, Nina Winkler, Klara Diester, Nicolas Gengenbacher, Rebekka Weber, Ihor Arkhypov, Samantha Lasser, Vera Petrova, Hellmut G. Augustin, Peter Altevogt, Jochen Utikal, Zvi G. Fridlender, Viktor Umansky
Summary: Myeloid-derived suppressor cells (MDSC) are a heterogeneous myeloid cell population expanded in tumor-bearing hosts and contribute to immunosuppression, making them a valuable therapeutic target. In melanoma, both polymorphonuclear (PMN) and monocytic (M) MDSC subsets have comparable immunosuppressive activities, with PMN-MDSC recruitment mediated by the CXCR2/CXCL1 axis. Inhibiting CXCR2 decreases PMN-MDSC infiltration, improves survival, and reduces metastasis, suggesting a critical role of PMN-MDSC in suppressing the NK cell-mediated anti-tumor response.
Article
Oncology
Qian Sun, Daniel Novak, Laura Hueser, Juliane Poelchen, Huizi Wu, Karol Granados, Aniello Federico, Ke Liu, Tamara Steinfass, Marlene Vierthaler, Viktor Umansky, Jochen Utikal
Summary: FOXD1 plays a role in regulating melanoma cell migration and invasion, with its upregulation associated with increased resistance of melanoma cells to drug treatment; through the regulation of FOXD1, CTGF can affect the sensitivity of melanoma cells to drug treatment.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Editorial Material
Oncology
Stefano Ugel, Vincenzo Bronte
Summary: The study reveals a novel pathway regulating the interaction between M-MDSCs and cancerous plasma cells in multiple myeloma.
CANCER IMMUNOLOGY RESEARCH
(2021)
Review
Oncology
Christopher Groth, Rebekka Weber, Samantha Lasser, Feyza Gul Ozbay, Annina Kurzay, Vera Petrova, Peter Altevogt, Jochen Utikal, Viktor Umansky
Summary: This review summarizes the origin of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) and their relation to classical neutrophils, outlining their metastasis promoting features and promising strategies for targeting them to enhance the efficacy of cancer immunotherapy.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Cell Biology
Ruslan B. Strutynskyi, Serhii Goncharov, Lesya Tumanovska, Vasyl S. Nagibin, Victor E. Dosenko
Summary: The study revealed the association between changes in K-ATP channel subunits and alterations in heart function and structure in spontaneously hypertensive rats, suggesting that the significant decrease in SUR2 expression may be one of the mechanisms of heart failure decompensation.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Oncology
Ludovica Arpinati, Naomi Kaisar-Iluz, Merav E. Shaul, Christopher Groth, Viktor Umansky, Zvi G. Fridlender
Summary: Neutrophils, an abundant type of circulating leukocytes, play crucial roles in cancer biology. This study reveals that tumor-associated neutrophils can originate from different subpopulations and exhibit plasticity under the influence of chemokines and tumor-derived factors, potentially transitioning through phenotypical changes.
Article
Multidisciplinary Sciences
Mitchell E. Fane, Yash Chhabra, Gretchen M. Alicea, Devon A. Maranto, Stephen M. Douglass, Marie R. Webster, Vito W. Rebecca, Gloria E. Marino, Filipe Almeida, Brett L. Ecker, Daniel J. Zabransky, Laura Huser, Thomas Beer, Hsin-Yao Tang, Andrew Kossenkov, Meenhard Herlyn, David W. Speicher, Wei Xu, Xiaowei Xu, Elizabeth M. Jaffee, Julio A. Aguirre-Ghiso, Ashani T. Weeraratna
Summary: The aged lung microenvironment provides a permissive niche for the growth and dissemination of melanoma cells, while age-related changes in the skin suppress melanoma growth but drive dissemination. Reprogramming of lung fibroblasts and activation of WNT5A promote the metastasis and dissemination of melanoma cells by inhibiting WNT5A in melanoma cells.
Article
Oncology
Rebekka Bitsch, Annina Kurzay, Feyza Oezbay Kurt, Carolina De la Torre, Samantha Lasser, Alisa Lepper, Alina Siebenmorgen, Verena Mueller, Peter Altevogt, Jochen Utikal, Viktor Umansky
Summary: STAT3 inhibitor Napabucasin can block the accumulation and activity of MDSC and improve the prognosis of patients with malignant melanoma. Patients with high expression of activated STAT3 in M-MDSC have shorter progression-free survival, indicating that STAT3 may be a promising therapeutic target in the treatment of malignant melanoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)