Article
Chemistry, Multidisciplinary
Qiong Li, Siyuan Qin, Hailong Tian, Ruolan Liu, Ling Qiao, Shanshan Liu, Bowen Li, Mei Yang, Jiayan Shi, Edouard C. Nice, Jingquan Li, Tingyuan Lang, Canhua Huang
Summary: A chemo-phototherapy nanoplatform is designed, in which econazole and biliverdin are co-assembled, improving the solubility of econazole and enhancing the efficacy of PD-L1 checkpoint blockade therapy against pancreatic ductal adenocarcinoma (PDAC).
Article
Oncology
Xiaobao Yang, Guanzheng Wang, Yue Song, Tongtao Zhuang, Yifei Li, Yujie Xie, Xuefeng Fei, Yanan Zhao, Dakang Xu, Yiqun Hu
Summary: Combining multiplex immunohistochemistry imaging and cytometry-based cell quantification, we can assess multiple lineage-selective and functional phenotypic biomarkers and analyze the relationship between immune complexity in the tumor microenvironment (TME) and clinical outcomes. Our study reveals that the percentage of CD8(+) T cells expressing the PD-1 exhaustion marker and/or high expression of the PD-L1 checkpoint in CD68(+) cells is associated with poor prognosis. This combined approach has a greater prognostic value than traditional cell density analyses. Additionally, there is a correlation between the abundance of PD-L1(+)CD68(+) tumor-associated macrophages and PD-1(+)CD8(+) T cell infiltration.
Article
Biotechnology & Applied Microbiology
Zhifang Zhang, Annie Yang, Shyambabu Chaurasiya, Anthony K. Park, Jianming Lu, Sang-In Kim, Susanne G. Warner, Yate-Ching Yuan, Zheng Liu, Haiyong Han, Daniel Von Hoff, Yuman Fong, Yanghee Woo
Summary: The study demonstrates that genetically modified oncolytic viruses can significantly upregulate PD-L1 expression in PDAC, and virus-delivered anti-PD-L1 antibodies can enhance anti-tumor immune killing in PDAC.
CANCER GENE THERAPY
(2022)
Article
Oncology
S. Mazher Hussain, Rita G. Kansal, Marcus A. Alvarez, T. J. Hollingsworth, Abul Elahi, Gustavo Miranda-Carboni, Leah E. Hendrick, Ajeeth K. Pingili, Lorraine M. Albritton, Paxton Dickson, Jeremiah L. Deneve, Danny Yakoub, D. Neil Hayes, Michio Kurosu, David Shibata, Liza Makowski, Evan S. Glazer
Summary: The study found that non-SMAD-TGF-beta signaling proteins, including pMAPK14, PD-L1, pAkt, and c-Myc, were elevated in tumors from patients with aggressive PDAC. Intervention with treatments such as gemcitabine and galunisertib led to decreased PD-L1 expression and reduced metastases in PDAC. Moreover, in mouse models, TGF-beta was found to increase TAMs-induced immunosuppression and PD-L1 expression in liver metastases.
Article
Oncology
Jiajin Li, Ruohua Chen, Yumei Chen, Qing Xia, Xiang Zhou, Qian Xia, Cheng Wang, Liangrong Wan, Haiqin Bao, Gang Huang, Jianjun Liu
Summary: This study investigated the usefulness of F-18-FDG PET/CT in evaluating the PD-L1 status in PDAC and found a correlation between high F-18-FDG uptake and high PD-L1 expression. It was also demonstrated that the JAK-STAT pathway plays an important role in mediating PD-L1's promotion of glucose uptake in PDAC.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Kelly E. Henry, Kyeara N. Mack, Veronica L. Nagle, Mike Cornejo, Adam O. Michel, Ian L. Fox, Maria Davydova, Thomas R. Dilling, Nagavarakishore Pillarsetty, Jason S. Lewis
Summary: The study shows that inhibition of MEK or ERK can increase PD-L1 expression, potentially enhancing anti-PD-L1 immune checkpoint therapy in PDAC. Furthermore, a combination of ERK inhibition and anti-PDL1 therapy significantly improved overall survival in a syngeneic mouse model of PDAC, with the survival benefit possibly being CD8(+) T-cell mediated. The therapeutic and molecular imaging tool kit developed in this study could be utilized to structure better clinical trials and address therapeutic gaps in challenging malignancies like PDAC.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Biotechnology & Applied Microbiology
Kang Sun, Xiaozhen Zhang, Mengyi Lao, Lihong He, Sicheng Wang, Hanshen Yang, Jian Xu, Jianghui Tang, Zhengtao Hong, Jinyuan Song, Chengxiang Guo, Muchun Li, Xinyuan Liu, Yan Chen, Hanjia Zhang, Jingxing Zhou, Jieru Lin, Sirui Zhang, Yifan Hong, Jinyan Huang, Tingbo Liang, Xueli Bai
Summary: Pancreatic ductal adenocarcinoma (PDAC) is resistant to immune checkpoint blockade therapy, but inhibiting leucine-rich repeat kinase 2 (LRRK2) can enhance the effectiveness of immunotherapy. LRRK2 inhibition increases the anti-cancer immune response in PDAC mice and sensitizes them to anti-PD-L1 therapy. This discovery suggests a new therapeutic strategy for PDAC.
Article
Immunology
Tina Daunke, Silje Beckinger, Sascha Rahn, Sandra Kruger, Steffen Heckl, Heiner Schafer, Daniela Wesch, Christian Pilarsky, Markus Eckstein, Arndt Hartmann, Christoph Rocken, Anna Maxi Wandmacher, Susanne Sebens
Summary: In pancreatic ductal adenocarcinoma (PDAC), tumor-associated macrophages express PD-L1 while PDAC cells do not. PD-L1 expression is high at the tumor invasion front between tumor-associated macrophages and CD8+ T cells. Treatment with immune checkpoint inhibitors (ICI) does not enhance the activation and cytotoxicity of CD8+ T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qing Xia, Jing Jia, Chupeng Hu, Jinying Lu, Jiajin Li, Haiyan Xu, Jianchen Fang, Dongju Feng, Liwei Wang, Yun Chen
Summary: This study found that TGF-beta 1 secreted by TAMs promotes the expression of PD-L1 in PDAC cells by inducing nuclear translocation of PKM2. The interaction between PKM2 and STAT1 enhanced by TGF-beta 1 stimulation facilitates the transactivation of PD-L1. Knockdown of PKM2 decreases PD-L1 expression, promotes NK cell activation, inhibits tumor growth, and when combined with PD-1/PD-L1 blockade, limits tumor growth.
Article
Cell Biology
Hua Guan, Kun Tian, Wei Luo, Mingfei Li
Summary: Emerging evidence suggests the crucial role of N-6-methyladenosine (m(6)A) modification in human cancers. This study identified a novel m(6)A-modified circRNA, circMYO1C, from the MYO1C gene, which was upregulated in pancreatic ductal adenocarcinoma (PDAC). CircMYO1C was found to be highly expressed in PDAC tissues, and its silencing reduced tumor growth. Mechanistically, circMYO1C cyclization was mediated by the m(6)A methyltransferase METTL3. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed significant m(6)A modification on PD-L1 mRNA, and circMYO1C targeted the m(6)A site of PD-L1 mRNA to enhance its stability through cooperation with IGF2BP2, accelerating PDAC immune escape.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Bryn Golesworthy, Yifan Wang, Amanda Tanti, Alain Pacis, Joan Miguel Romero, Adeline Cuggia, Celine Domecq, Guillaume Bourdel, Robert E. Denroche, Gun Ho Jang, Robert C. Grant, Ayelet Borgida, Barbara T. Grunwald, Anna Dodd, Julie M. Wilson, Guillaume Bourque, Grainne M. O'Kane, Sandra E. Fischer, Chelsea Maedler Kron, Pierre-Olivier Fiset, Atilla Omeroglu, William D. Foulkes, Steven Gallinger, Marie-Christine Guiot, Zu-Hua Gao, George Zogopoulos
Summary: This study investigated the immune contexture of HR-d PDAC using multiplex immunohistochemistry. The results showed higher infiltration of intra-tumoral CD8+ T-cells and increased FOXP3+ Tregs in HR-d PDAC compared to HR/MMR-intact PDAC. Additionally, PD-L1 positivity was observed in a subset of HR-d PDAC cases. These findings suggest that HR-d PDAC may be responsive to immune checkpoint inhibitor treatment strategies.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Qian Zhu, Guoliang Qiao, Lefu Huang, Chang Xu, Deliang Guo, Shuo Wang, Jing Zhao, Yuguang Song, Bing Liu, Zheng Chen, Zhiyong Yang, Yufeng Yuan
Summary: This study aimed to investigate the relationship between the restoration of CD8(+)PD-1(+) T cells through adoptive T-cell therapy (ACT) and the prognosis and therapeutic response to anti-PD-1 in patients with advanced pancreatic cancer (APC). The results showed that the CD8(+)PD-1(+) T-cell level was related to the expression of PD-L1. Restoring CD8(+)PD-1(+) T cells through ACT significantly improved the prognosis and facilitated the response to anti-PD-1 in APC patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T. Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A. Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D. Jewell, Galen Hostetter, Chelsea J. Newton, Qing Kay Li, Michael H. Roehr, David Fenyo, Pei Wang, Alexey Nesvizhskii, D. R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang
Summary: This study conducted comprehensive proteogenomic analysis of PDAC to understand the molecular alterations that drive oncogenesis. Multiple analyses were performed on tissues from patients, providing valuable resources for early detection and identification of therapeutic targets.
Review
Biochemistry & Molecular Biology
Nausika Betriu, Juan Bertran-Mas, Anna Andreeva, Carlos E. Semino
Summary: Syndecans, a subfamily of proteoglycans, play critical roles in various physiological processes and have implications in disease progression. Their interactions with other macromolecules contribute to normal cellular functions and disease pathogenesis.
Article
Medicine, General & Internal
Zhiwei Zhang, Qunli Xiong, Yongfeng Xu, Xuebin Cai, Lisha Zhang, Qing Zhu
Summary: The tumor microenvironment (TME) is crucial for the development, progression, and metastasis of pancreatic cancer (PC), especially in adenosquamous carcinoma of pancreas (ASCP). The expression of CD3, CD4, CD8, FoxP3, and PD-L1 within the TME was studied, and their correlation with the prognosis of PC was identified. Higher levels of PD-L1 were associated with shorter overall survival in ASCP and PDAC patients, while higher infiltration of CD3+ and CD8+ T-cells was significantly correlated with better prognosis in PC.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Wentao Liu, Bin Yan, Haixin Yu, Jiannan Ren, Mou Peng, Liang Zhu, Yinhuai Wang, Xin Jin, Lu Yi
Summary: This study investigates the clinicopathological role of the OTUD family in ccRCC and identifies that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Oncology
Hongkun Cai, Feng Guo, Shuang Wen, Xin Jin, Heshui Wu, Dianyun Ren
Summary: The study found that abnormal KRAS activation in pancreatic cancer led to ITGA2 overexpression, which in turn suppressed the activation of the TGF-beta pathway. Mechanistically, ITGA2 inhibited the activation of the TGF-beta pathway by transcriptionally inhibiting SMAD2 expression. Additionally, ITGA2 interacted with TFCP2, inhibiting its nuclear translocation and affecting the expression of SMAD2.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Wentao Liu, Dianyun Ren, Wei Xiong, Xin Jin, Liang Zhu
Summary: Our study identified that NFAT1, when overexpressed in RCC, was associated with poor prognosis and could enhance tumor growth by increasing PD-L1 expression. Additionally, NFAT1 was found to be stabilized in sunitinib-resistant RCC through hyperactivation of the PI3K/AKT/GSK-3 beta signaling pathway. The downregulation of FBW7, which promotes NFAT1 degradation, was induced by FOXA1 and SETD2 in sunitinib-resistant RCC, contributing to immune response modulation. This study reveals a new role for the FBW7/NFAT1 axis in RCC response to TKIs and ICIs, suggesting NFAT1 as a potential therapeutic target for RCC treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Xiang Cheng, Bin Zhang, Feng Guo, Heshui Wu, Xin Jin
Summary: PARP inhibitors increase double-stranded breaks in DNA and are particularly effective in tumors with BRCA mutations. The study shows that FBP1 regulates sensitivity to PARP inhibitors in pancreatic cancer, while USP7 inhibitors enhance the antitumor effect of PARP inhibitors in an FBP1-dependent manner. These findings suggest a potential new treatment strategy for pancreatic cancer patients.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Dianyun Ren, Yan Sun, Dan Li, Heshui Wu, Xin Jin
Summary: PTEN is a dual lipid and protein phosphatase that plays a crucial role in pancreatic cancer. USP22 has been identified as a novel modifying enzyme of PTEN, enhancing p21 expression and inhibiting cancer progression. Moreover, ANKHD1 and MDM2 could be potential therapeutic targets for pancreatic cancer treatment.
MOLECULAR ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xin Jin, Bin Zhang, Hao Zhang, Haixin Yu
Summary: The study identified that smoking-induced upregulation of CBX3 promotes lung adenocarcinoma progression by activating the ARHGAP24/Rac1 pathway, suggesting the CBX3/ARHGAP24/Rac1 axis as a potential therapeutic target for smoking-induced LUAD.
Article
Oncology
Jiannan Ren, Haixin Yu, Wei Li, Xin Jin, Bin Yan
Summary: This study revealed that CBX7 is downregulated in bladder cancer and EZH2 represses CBX7 expression through increased H3K27me3. Additionally, CBX7 directly downregulates FGFR3 expression and sensitizes bladder cancer cells to cisplatin treatment.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Yapeng Wang, Mou Peng, Yawen Zhong, Wei Xiong, Liang Zhu, Xin Jin
Summary: This study identified that elevated levels of E3 ligase RBCK1 contribute to the resistance of ccRCC cells to sunitinib, a targeted tyrosine kinase inhibitor. Inhibition of RBCK1 increased sensitivity to sunitinib and inactivated the AKT and MAPK signaling pathways. Mechanistically, RBCK1 promotes the degradation of ANKRD35 and destabilizes MITD1, leading to dysregulation of sunitinib in ccRCC cells.
Article
Cell Biology
Chong Yang, Xin Jin, Xingchao Liu, Gang Wu, Wenhao Yang, Beichuan Pang, Jipeng Jiang, Dongxu Liao, Yu Zhang
Summary: Systemic therapy is the standard treatment for advanced or metastatic Hepatocellular carcinoma (HCC) patients who are not eligible for surgical resection. However, resistance to tyrosine kinase inhibitors (TKIs) eventually develops in all responders. In this study, it was found that TRIM15, an E3 ligase, was abnormally upregulated in liver cancer cells after TKI treatment, contributing to TKI resistance. The upregulation of TRIM15 was mediated by the AKT/FOXO1 axis and it induced the nuclear translocation of LASP1, resulting in increased AKT phosphorylation and Snail expression, and modulated TKI sensitivity in liver cancer cells.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Yan Sun, Liang Zhu, Pian Liu, Huan Zhang, Feng Guo, Xin Jin
Summary: In this study, researchers found that the upregulation of palmitoyl acyltransferase ZDHHC2 is associated with TKI resistance in ccRCC. ZDHHC2 mediates AGK S-palmitoylation to activate the PI3K-AKT-mTOR signaling pathway, which modulates sunitinib sensitivity. These findings suggest that targeting ZDHHC2 may improve the efficacy of sunitinib in treating ccRCC.
Article
Biochemistry & Molecular Biology
Yan Sun, Xin Jin, Junpeng Meng, Feng Guo, Taoyu Chen, Xiaoyan Zhao, Heshui Wu, Dianyun Ren
Summary: PRMT5 contributes to the inactivation of the Hippo signaling pathway in pancreatic cancer by blocking the homodimerization of MST2 through symmetrical dimethylation. Inhibitors of PRMT5 can reactivate the dysregulated Hippo signaling pathway and inhibit the growth of pancreatic cancer.
Article
Biochemistry & Molecular Biology
Bin Yan, Xurui Li, Mou Peng, Yali Zuo, Yinhuai Wang, Pian Liu, Weigang Ren, Xin Jin
Summary: Understanding the relationship between glucose metabolism and bladder cancer can potentially lead to new therapies. Researchers found that a protein called YTHDC1, which is suppressed by high blood sugar, is associated with poor prognosis in bladder cancer. Increasing YTHDC1 levels can slow tumor growth by reducing sugar input through the glucose transporter GLUT3. These findings provide insights into how high blood sugar promotes bladder cancer growth and may lead to the development of new drugs.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Huaiyuan Liang, Chunguang Yang, Ruijiang Zeng, Yingqiu Song, Jianxi Wang, Wei Xiong, Binyuan Yan, Xin Jin
Summary: This study found that CBX3 is transcriptionally upregulated by BRD4 in castration-resistant prostate cancer (CRPC) cells, and PLK1 phosphorylates CBX3 to affect its interaction with RB1, leading to decreased sensitivity of cells to CDK4/6 inhibitors. Therefore, a dual BRD4/PLK1 inhibitor may partially increase sensitivity to CDK4/6 inhibitors in CRPC cells through CBX3.
Article
Biochemistry & Molecular Biology
Huan Zhang, Haixin Yu, Dianyuan Ren, Yan Sun, Feng Guo, Hongkun Cai, Chen Zhou, Yingke Zhou, Xin Jin, Heshui Wu
Summary: Tobacco smoking induces epigenetic modifications to promote pancreatic cancer development, with CBX3 acting as a key regulator in this process.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Wentao Liu, Haohui Wang, Chengzhu Jian, Wei Li, Kun Ye, Jiannan Ren, Liang Zhu, Yinhuai Wang, Xin Jin, Lu Yi
Summary: In this study, the downregulation of CBX7 in ccRCC was found to be associated with favorable prognosis. CBX7 inhibits cancer cell proliferation and invasion, and inactivates the TNF signaling pathway by inhibiting ETS1 expression. A novel RNF26/CBX7 axis was discovered, which modulates the TNF signaling pathway in ccRCC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
