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Crosstalk between IL-15Rα^(+)tumor-associated macrophages and breast cancer cells reduces CD8+T cell recruitment

Cancer Communications 2022年第6期42卷 536-557页

作者： Wenlong Zhang Qing Zhang Nanfei Yang Qian Shi Huifang Su Tingsheng Lin Zhonglei He Wenxin Wang Hongqian Guo Pingping Shen State key Laboratory of Pharmaceutical Biotechnology and Department of Urology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolSchool of Life SciencesNanjing UniversityNanjingJiangsu 210023P.R.China Department of Urology Drum Tower HospitalMedical School of Nanjing UniversityInstitute of UrologyNanjing UniversityNanjingJiangsu 210008P.R.China Shenzhen research Institute of Nanjing University Shenzhen 518000China Department of Cellular and Integrative Physiology The University of Texas Health Science Center at San AntonioSan AntonioTexas 78229-3904USA Charles Institute of Dermatology School of MedicineUniversity College DublinDublin Eircode D04 V1W8Ireland

Background:Interleukin-15(IL-15)is a promising immunotherapeutic agent owing to its powerful immune-activating effects.However,the clinical benefits of these treatments are limited.Crosstalk between tumor cells and immune cells plays an important role in immune escape and immunotherapy drug resistance.Herein,this study aimed to obtain in-depth understanding of crosstalk in the tumor microenvironment for providing potential therapeutic strategies to prevent tumor progression.Methods:T-cell killing assays and co-culture models were developed to determine the role of crosstalk between macrophages and tumor cells in breast cancer resistant to IL-15.Western blotting,histological analysis,CRISPR-Cas9 knockout,multi-parameter flow cytometry,and tumor cell-macrophage co-injection mouse models were developed to examine the mechanism by which IL-15Rα^(+)tumor-associated macrophages(TAMs)regulate breast cancer cell resistance to IL-15.Results:We found thatmacrophages contributed to the resistance of tumor cells to IL-15,and tumor cells induced macrophages to express high levels of theαsubunit of the IL-15 receptor(IL-15Rα).Further investigation showed that IL-15Rα^(+)TAMs reduced the protein levels of chemokine CX3C chemokine ligand 1(CX3CL1)in tumor cells to inhibit the recruitment of CD8^(+)T cells by releasing the IL-15/IL-15Rαcomplex(IL-15Rc).Administration of an IL-15Rc blocking peptide markedly suppressed breast tumor growth and overcame the resistance of cancer cells to anti-programmed cell death protein 1(PD-1)antibody immunotherapy.Interestingly,Granulocyte-macrophage colony-stimulating factor(GMCSF)inducedγchain(γc)expression to promote tumor cell-macrophage crosstalk,which facilitated tumor resistance to IL-15.Additionally,we observed that the non-transcriptional regulatory function of hypoxia inducible factor-1alpha(HIF-1α)was essential for IL-15Rc to regulateCX3CL1 expression in tumor cells.Conclusions:The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the t

关键词： breast cancer CD8^(+)T-cell crosstalk IL-15Rα immunotherapy tumor microenvironment tumor-associated macrophages

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Anode interfacial modification for non-fullerene polymer solar cells:Recent advances and prospects

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InfoMat 2022年第12期4卷 33-73页

作者： Nafees Ahmad Guangxing Liang Ping Fan Huiqiong Zhou Shenzhen key Laboratory of Advanced Thin Films and Applications Key Laboratory of Optoelectronic Devices and SystemsCollege of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhenPeople's Republic of China CAS key Laboratory of Nanosystem and Hierarchical Fabrication National Center for Nanoscience and TechnologyBeijingPeople's Republic of China

Recently,the power conversion efficiency(PCE)of single-junction non-fullerene polymer solar cells(NF-PSCs)has surpassed 19%due to the fast development of novel donor polymers,NF-acceptors,device engineering,and interlayer materials.The anode interlayer(AIL)plays a vital role in improving the efficiency and stability of PSCs.The challenges and opportunities in this research area encourage researchers to pursue great innovation in developing new materials and strategies for highly efficient NF-PSCs.This review summarizes the recent development of AIL materials and their modification strategies in single-junction NF-PSCs.Firstly,a brief introduction,key functions,basic requirements,and peculiar features of AILs when employed in NF-PSCs are discussed.Then,the impact of AIL materials(including organic,inorganic,and hybrid materials)on the PCE and the stability of NF-PSCs are described.Afterward,the fabrication of large-area devices and related issues are highlighted.The summary and the future challenges regarding efficient AIL are summarized in the last section of this review.

关键词： anode interlayer efficiency hole extraction non-fullerene polymer solar cells stability

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