Article
Cell Biology
Tian-Tian Liu, Feiya Ou, Julia A. Belk, Prachi Bagadia, David A. Anderson III, Vivek Durai, Winnie Yao, Ansuman T. Satpathy, Theresa L. Murphy, Kenneth M. Murphy
Summary: In this study, the researchers found that different elements within the Irf8 superenhancer have cooperative or temporal effects on dendritic cell development. They discovered that the +41-kb enhancer is required for pre-cDC1 specification, while the +32-kb enhancer is necessary for cDC1 maturation. They also demonstrated that the +32-kb enhancer is dependent on the +41-kb enhancer, and that the activation of the +32-kb enhancer is controlled by chromatin accessibility and transcription factor binding.
GENES & DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Wei-Wei Luo, Zhen Tong, Pan Cao, Fu-Bing Wang, Ying Liu, Zhou-Qin Zheng, Su-Yun Wang, Shu Li, Yan-Yi Wang
Summary: The transcription-independent function of IRF8 mediates STING activation and represents an important regulatory step in the cGAS/STING innate immune pathway in monocytes.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Benita C. Y. Tse, Sarah Bergamin, Pascal Steffen, George Hruby, Nick Pavlakis, Stephen J. Clarke, Justin Evans, Alexander Engel, Andrew Kneebone, Mark P. Molloy
Summary: By analyzing the immunophenotype of rectal cancer diagnostic biopsies from 16 LARC patients treated with CRT, it was found that patients with greater tumor regression had higher infiltration of pan-T cells and IRF8(+)HLA-DR+ cells prior to CRT. High density of IRF8(+)HLA-DR+ cells was associated with 83% survival at 5 years, while low infiltration of CD11c(+) myeloid cells was associated with longer 3- and 5-year disease-free survival. These findings suggest that measuring IRF8(+) HLA-DR+ cells and CD11c(+) myeloid cells in rectal cancer biopsies can predict CRT-induced tumor regression and survival in LARC patients.
Review
Pharmacology & Pharmacy
Ahmed O. Elzoghby, Cristina R. Ferrone, Soldano Ferrone, Mahmoud L. Nasr
Summary: Pancreatic cancer is a highly aggressive and resistant type of cancer. This review highlights the recent advances in engineering nanomedicines to enhance the immune response against pancreatic cancer. Nanomedicines are used to increase the immunogenicity of cancer cells, deactivate cancer-associated fibroblasts, enhance the antigen-presenting capacity of dendritic cells, reverse the immunosuppressive nature of the tumor microenvironment, and improve the infiltration of cytotoxic T lymphocytes for efficient antitumor immune responses.
DRUG DISCOVERY TODAY
(2023)
Article
Biochemistry & Molecular Biology
Alice Clare Newman, Mattia Falcone, Alejandro Huerta Uribe, Tong Zhang, Dimitris Athineos, Matthias Pietzke, Alexei Vazquez, Karen Blyth, Oliver David Kenneth Maddocks
Summary: Cancer cells adapt their metabolism to meet the increased demands for synthesis. Recent research has focused on nutrients that supply one-carbon units to the folate cycle, particularly serine. Tryptophan can serve as a theoretical source of one-carbon units through metabolism by IDO1, and cancer cells release tryptophan-derived formate that can be utilized by other cells.
Article
Immunology
Na Li, Stefanie Steiger, Lingyan Fei, Chenyu Li, Chongxu Shi, Natallia Salei, Barbara U. Schraml, Zhihua Zheng, Hans-Joachim Anders, Julia Lichtnekert
Summary: Our study found that IRF8 is essential for kidney cDC1s, which have a mild protective effect against post-ischemic AKI/AKD, possibly by suppressing tissue inflammation and damage, indicating an immunoregulatory role for cDC1s.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Joyce Lee, Filomena Housley, Christina Yau, Rachel Nakagawa, Juliane Winkler, Johanna M. Anttila, Pauliina M. Munne, Mariel Savelius, Kathleen E. Houlahan, Daniel Van de Mark, Golzar Hemmati, Grace A. Hernandez, Yibing Zhang, Susan Samson, Carole Baas, Laura J. Esserman, Laura J. van 't Veer, Hope S. Rugo, Christina Curtis, Juha Klefstrom, Mehrdad Matloubian, Andrei Goga
Summary: This study reveals that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy, but this resistance can be overcome by restoring interferon signaling and targeting specific molecules. This finding has important implications for improving the outcomes of patients with TNBC treated with immune checkpoint inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Annesa Das, Kuldeep Singh Chauhan, Himanshu Kumar, Prafullakumar Tailor
Summary: The study uncovered the distinct roles of IRF8 in regulating the development of cDC1 and modulating the functionality of pDCs, without affecting development.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Alba Navarro-Ocon, Jose L. Blaya-Canovas, Araceli Lopez-Tejada, Isabel Blancas, Rosario M. Sanchez-Martin, Maria J. Garrido, Carmen Grinan-Lison, Jesus Calahorra, Francisca E. Cara, Francisco Ruiz-Cabello, Juan A. Marchal, Natalia Aptsiauri, Sergio Granados-Principal
Summary: Breast cancer is the most common type of malignancy among women worldwide, but clinical response to immunotherapy is often below expectations due to immune escape mechanisms. Nanomedicine presents an opportunity to enhance the efficacy of cancer immunotherapy and overcome tumor immune escape.
Article
Oncology
Bhuwan Giri, Prateek Sharma, Tejeshwar Jain, Anthony Ferrantella, Utpreksha Vaish, Siddharth Mehra, Bharti Garg, Srikanth Iyer, Vrishketan Sethi, Zoe Malchiodi, Rossana Signorelli, Harrys K. C. Jacob, John George, Preeti Sahay, Ejas P. Bava, Rajinder Dawra, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja
Summary: The absence of Hsp70 in the tumor microenvironment inhibits tumor growth through immune cells, and Hsp70(-/-) dendritic cells inhibit tumor growth by enhancing the immune response.
Article
Multidisciplinary Sciences
Xuezhi Cao, Yong Liang, Zhenxiang Hu, Huiyu Li, Jiaming Yang, Eric J. Hsu, Jiankun Zhu, Jin Zhou, Yang-Xin Fu
Summary: The study introduces a novel masked IFN-I prodrug activated by tumor-associated proteases, which enhances anti-tumor immune response with reduced toxicity and improved tumor targeting. This engineered prodrug shows prolonged serum half-life, improved tumor-targeting effect, enhanced DC cross-priming, increased CD8(+) infiltration and effector function in the tumor microenvironment, as well as improved checkpoint blockade and radiation efficacy for tumors. Overall, this effective tumor-activating IFN has promising long-term pharmacokinetics with minimal toxicity.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Zhe Chen, Chaoyang Meng, Junhua Mai, Yongbin Liu, Hangwen Li, Haifa Shen
Summary: This study demonstrates that a lipid-formulated RNA vaccine composed of a protamine/mRNA core and a lipid shell is highly effective in promoting cytotoxic CD8 T cell responses and mediating anti-tumor immunity. Both the mRNA core and lipid shell are necessary for stimulating the expression of type I interferons and inflammatory cytokines in dendritic cells. The expression of interferon relies exclusively on STING, and the antitumor activity of the mRNA vaccine is compromised in mice with a defective Sting gene. Thus, the mRNA vaccine induces STING-dependent antitumor immunity.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Cell Biology
Khaled Zubeidat, Yasmin Jaber, Yasmin Saba, Or Barel, Reem Naamneh, Yasmin Netanely, Yael Horev, Luba Eli-berchoer, Amjad Shhadeh, Omri Yosef, Eliran Arbib, Gili Betser-Cohen, Chen Nadler, Hagit Shapiro, Eran Elinav, Doron J. Aframian, Asaf Wilensky, Avi-Hai Hovav
Summary: This study investigates the postnatal mechanisms in the salivary glands that establish immunity. High levels of neutrophils and transferred maternal IgG are present temporarily in neonatal murine salivary glands, independent of the microbiota. During weaning, neutrophils, FcRn, and IgG decrease while pIgR is upregulated in a GAS6-dependent manner, independent of the microbiota. Salivary IgA production begins following weaning and requires CD4-help, IL-17, and the microbiota. This study suggests that salivary glands play a role as an immune inductive site.
Review
Medicine, Research & Experimental
Da Qian, Jialu Li, Mingyao Huang, Qiuxia Cui, Xiaozhen Liu, Kailv Sun
Summary: Breast cancer is the most common cancer in women worldwide. Immunotherapy, including tumor vaccine, has shown great success in treating breast cancer. Dendritic cells are important antigen-presenting cells that play a role in immune responses. DC-based treatments, particularly DC vaccines, have demonstrated significant anti-tumor effects in clinical studies and are undergoing trials. This review summarizes the immunomodulatory effects of DC vaccines in breast cancer, discusses related mechanisms, and presents possible challenges and future directions.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Xiang Ma, Junlong Guo, Cuiting Zhang, Jinfeng Bai
Summary: This study found that marital status can affect the overall survival of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and developed a prognostic nomogram to predict survival outcomes. Marital status was identified as an independent prognostic factor and the nomogram showed moderate influence in predicting survival.
SCIENTIFIC REPORTS
(2022)
Article
Gastroenterology & Hepatology
Hong Jiang, Xiuting Liu, Brett L. Knolhoff, Samarth Hegde, Kyung Bae Lee, Hongmei Jiang, Ryan C. Fields, Jonathan A. Pachter, Kian-Huat Lim, David G. DeNardo
Article
Immunology
Prakash Babu Narasimhan, Tobias Eggert, Yanfang Peipei Zhu, Paola Marcovecchio, Melissa A. Meyer, Runpei Wu, Catherine C. Hedrick
JOURNAL OF IMMUNOLOGY
(2020)
Article
Pathology
Ivan A. Gonzalez, Liang- Kang, Gregory A. Williams, Jingxia Liu, David G. DeNardo, William G. Hawkins, Deyali Chatterjee
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2020)
Article
Oncology
Bhalchandra Mirlekar, Daniel Michaud, Samuel J. Lee, Nancy P. Kren, Cameron Harris, Kevin Greene, Emily C. Goldman, Gaorav P. Gupta, Ryan C. Fields, William G. Hawkins, David G. DeNardo, Naim U. Rashid, Jen Jen Yeh, Autumn J. McRee, Benjamin G. Vincent, Dario A. A. Vignali, Yuliya Pylayeva-Gupta
CANCER IMMUNOLOGY RESEARCH
(2020)
Article
Oncology
Samarth Hegde, Varintra E. Krisnawan, Brett H. Herzog, Chong Zuo, Marcus A. Breden, Brett L. Knolhoff, Graham D. Hogg, Jack P. Tang, John M. Baer, Cedric Mpoy, Kyung Bae Lee, Katherine A. Alexander, Buck E. Rogers, Kenneth M. Murphy, William G. Hawkins, Ryan C. Fields, Carl J. DeSelm, Julie K. Schwarz, David G. DeNardo
Article
Immunology
Huy Q. Dinh, Tobias Eggert, Melissa A. Meyer, Yanfang Peipei Zhu, Claire E. Olingy, Ryan Llewellyn, Runpei Wu, Catherine C. Hedrick
Article
Medicine, Research & Experimental
Yongjia Li, Xinming Su, Nidhi Rohatgi, Yan Zhang, Jonathan R. Brestoff, Kooresh Shoghi, Yalin Xu, Clay F. Semenkovich, Charles A. Harris, Lindsay L. Peterson, Katherine N. Weilbaecher, Steven L. Teitelbaum, Wei Zou
Review
Oncology
Xiuting Liu, Graham D. Hogg, David G. DeNardo
Summary: The success of checkpoint inhibitors in cancer treatment has highlighted the importance of the immune system, particularly in eliciting antitumor responses. While initially thought to primarily target T cells, recent research suggests that these inhibitors may also impact innate immunity, thus playing a significant role in clinical efficacy. Further investigation into the mechanisms of action of checkpoint therapies on innate antitumor responses is crucial for developing effective combination treatments to combat checkpoint resistance in refractory malignancies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Gregory C. Fox, Xinming Su, Jennifer L. Davis, Yalin Xu, Kristin A. Kwakwa, Michael H. Ross, Francesca Fontana, Jingyu Xiang, Alison K. Esser, Elizabeth Cordell, Kristen Pagliai, Ha X. Dang, Jothilingam Sivapackiam, Sheila A. Stewart, Christopher A. Maher, Suzanne J. Bakewell, James A. J. Fitzpatrick, Vijay Sharma, Samuel Achilefu, Deborah J. Veis, Gregory M. Lanza, Katherine N. Weilbaecher
Summary: Breast cancer bone metastases are commonly incurable, with tumoral integrin β3 expression influenced by the bone microenvironment. High β3 expression is associated with poor outcomes in triple-negative breast cancer patients both before and after chemotherapy. Additionally, the study suggests mTORC1 inhibition combined with docetaxel can enhance the treatment efficacy in bone metastases.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Cell Biology
Roman Uzhachenko, Vijaya Bharti, Zhufeng Ouyang, Ashlyn Blevins, Stacey Mont, Nabil Saleh, Hunter A. Lawrence, Chengli Shen, Sheau-Chiann Chen, Gregory D. Ayers, David G. DeNardo, Carlos Arteaga, Ann Richmond, Anna E. Vilgelm
Summary: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) delay metastatic breast cancer progression, while also enhancing the efficacy of T cell-based therapies by inducing chemokines that recruit activated CD8(+) T cells to the tumor. The metabolic stress induced by CDK4/6i treatment in breast cancer cells plays a key role in this process, suggesting a link between tumor metabolic vulnerabilities and anti-tumor immunity.
Correction
Cell Biology
Roman V. Uzhachenko, Vijaya Bharti, Zhufeng Ouyang, Ashlyn Blevins, Stacey Mont, Nabil Saleh, Hunter A. Lawrence, Chengli Shen, Sheau-Chiann Chen, Gregory D. Ayers, David G. DeNardo, Carlos Arteaga, Ann Richmond, Anna E. Vilgelm
Article
Oncology
Francesca Fontana, Jingyu Xiang, Xinming Su, Eric Tycksen, Rachel Nassau, Gregory Fox, Giulia Leanza, Katherine Weilbaecher, Roberto Civitelli
Summary: Expression of the cell-cell adhesion molecule N-cadherin is associated with aggressive cancers, but its role in bone metastasis and extra-skeletal tumor formation is unclear.
JOURNAL OF BONE ONCOLOGY
(2021)
Article
Virology
Jingyu Xiang, Mijia Lu, Min Shi, Xiaogang Cheng, Kristin A. Kwakwa, Jennifer L. Davis, Xinming Su, Suzanne J. Bakewell, Yuexiu Zhang, Francesca Fontana, Yalin Xu, Deborah J. Veis, John F. DiPersio, Lee Ratner, Ralph D. Sanderson, Alessandro Noseda, Shamim Mollah, Jianrong Li, Katherine N. Weilbaecher
Summary: This study demonstrates that heparanase is a potential target for the pathogenesis of SARS-CoV-2 and that Roneparstat may serve as a dual-targeted therapy to reduce viral infection and inflammation in COVID-19.
JOURNAL OF VIROLOGY
(2022)
Article
Medicine, Research & Experimental
Xinming Su, Yalin Xu, Gregory C. Fox, Jingyu Xiang, Kristin A. Kwakwa, Jennifer L. Davis, Jad Belle, Wen-Chih Lee, Wing H. Wong, Francesca Fontana, Leonel F. Hernandez-Aya, Takayuki Kobayashi, Helen M. Tomasson, Junyi Su, Suzanne J. Bakewell, Sheila A. Stewart, Christopher Egbulefu, Partha Karmakar, Melisa A. Meyer, Deborah J. Veis, David G. DeNardo, Gregory M. Lanza, Samuel Achilefu, Katherine N. Weilbaecher
Summary: Tumor-infiltrating myeloid cells, induced by breast tumor cell-derived GM-CSF, contribute to an immunosuppressive microenvironment in breast cancer through the regulation of myeloid cell ARG1 expression. Targeting GM-CSF could enhance breast cancer immunotherapy by reversing immune suppression.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Erik Sahai, Igor Astsaturov, Edna Cukierman, David G. DeNardo, Mikala Egeblad, Ronald M. Evans, Douglas Fearon, Florian R. Greten, Sunil R. Hingorani, Tony Hunter, Richard O. Hynes, Rakesh K. Jain, Tobias Janowitz, Claus Jorgensen, Alec C. Kimmelman, Mikhail G. Kolonin, Robert G. Maki, R. Scott Powers, Ellen Pure, Daniel C. Ramirez, Ruth Scherz-Shouval, Mara H. Sherman, Sheila Stewart, Thea D. Tlsty, David A. Tuveson, Fiona M. Watt, Valerie Weaver, Ashani T. Weeraratna, Zena Werb
NATURE REVIEWS CANCER
(2020)