Article
Chemistry, Multidisciplinary
Jiwoong Choi, Man Kyu Shim, Suah Yang, Hee Sook Hwang, Hanhee Cho, Jeongrae Kim, Wan Su Yun, Yujeong Moon, Jinseong Kim, Hong Yeol Yoon, Kwangmeyung Kim
Summary: Immune checkpoint blockade is a promising approach for cancer immunotherapy, but many patients do not respond due to the immunosuppressive tumor microenvironment. This study proposes visible-light-triggered prodrug nanoparticles (LT-NPs) to reverse the immunosuppressive tumor microenvironment and enhance checkpoint blockade immunotherapy, showing promising results in tumor models.
Article
Medicine, Research & Experimental
Yujeong Moon, Man Kyu Shim, Jiwoong Choi, Suah Yang, Jinseong Kim, Wan Su Yun, Hanhee Cho, Jung Yeon Park, Yongju Kim, Joon-Kyung Seong, Kwangmeyung Kim
Summary: In this study, the researchers propose a new strategy to enhance cancer immunotherapy by using anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs). The PD-NPs are taken up by cancer cells and release the drug, resulting in the disruption of immune-suppressing pathways and the enhancement of T lymphocyte immune responses. The results show that PD-NPs accumulate in tumor tissues and recruit a large amount of immune cells, leading to effective antitumor effects. This strategy has the potential to overcome the toxicity and low response rate issues in current cancer immunotherapy.
Article
Oncology
Yuting Tang, Qian Xu, Liang Hu, Xiaomei Yan, Xiaomin Feng, Asumi Yokota, Weinan Wang, Di Zhan, Durga Krishnamurthy, David E. Ochayon, Lijun Wen, Li Huo, Huimin Zeng, Yingwan Luo, Mark Wunderlich, Jiwang Zhang, Eric Vivier, Jianfeng Zhou, Stephen N. Waggoner, Gang Huang
Summary: R-spondin 3 expression is associated with favorable prognosis and enhances infiltration and function of NK cells and T cells in tumors, leading to tumor regression, and also increases tumor sensitivity to anti-PD-1 therapy.
Article
Oncology
Shengchen Su, Sungyong You, Yanping Wang, Patrick Tamukong, Michael J. Quist, Catherine S. Grasso, Hyung L. Kim
Summary: Antitumor immunity requires lymphocytes to localize to the tumor. Prostate cancers (PCs) are immunologically cold and tend to lack T-cell infiltration. Most advanced PCs are insensitive to PD1 blockade therapies.
Review
Chemistry, Multidisciplinary
Elham Masoumi, Sahar Tahaghoghi-Hajghorbani, Leila Jafarzadeh, Mohammad-Javad Sanaei, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: This review provides an overview of the current research status of immune checkpoint blockades in breast cancer and discusses the efficacy and limitations of ICB therapy in breast cancer treatment.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Xiaowei Liu, Yanlin Feng, Jie Xu, Ying Shi, Jiqiao Yang, Rongjie Zhang, Jinen Song, Xin Bai, Xi Wu, Yu Bao, Ya Luo, Huifang Li, Li Chai, Changyang Gong, Yan Wang, Bo Chen, Jianping Hu, Yan Fu, Yongzhang Luo, Haiyuan Zhang, Hubing Shi
Summary: The research demonstrates the advantage of photothermal-targeted-immune triple combinatorial regimen in treating tumors that are clinically unresectable multifocal and lack T-cell infiltration.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Guiyuan Chen, Xiangxia Li, Rui Li, Kecheng Wu, Zhouhang Lei, Ruike Dai, Kyle Roche, Andrew Z. Wang, Yuanzeng Min
Summary: Researchers hypothesized that treating cancer cells with ultrahigh doses of chemotherapeutics in vitro could artificially enhance the immunogenicity, thereby improving chemoimmunotherapy.
Review
Immunology
Mohammad Hossein Kazemi, Alireza Najafi, Jafar Karami, Foad Ghazizadeh, Hassan Yousefi, Reza Falak, Elahe Safari
Summary: Recent advancements in cancer immunotherapy, particularly immune checkpoint (IC) blockers, have shown promising results in clinical settings. Immunometabolism plays a crucial role in regulating immune responses, and dual targeting of ICs and metabolic pathways may help restore immune cells' antitumor activity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Pavlos Msaouel, Giannicola Genovese, Jianjun Gao, Suvajit Sen, Nizar M. Tannir
Summary: Immune checkpoint inhibitors have shown promise in cancer treatment but are not always long-lasting and effective for all patients. Targeting TAM kinases with tyrosine kinase inhibitors may enhance the efficacy of immune checkpoint blockade, but whether selective targeting of each TAM receptor or multi-receptor TAM inhibitors are more effective remains to be determined. Triple inhibition of all TAM receptors may lead to increased risk of adverse events, and clinical trial designs should focus on determining the synergistic effects of combining TAM inhibition with immune checkpoint blockade through high-resolution clinical endpoints and proper control arms.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Immunology
Qi-jie Zhang, Jiao-chen Luan, Le-bin Song, Rong Cong, Cheng-jian Ji, Xiang Zhou, Jia-dong Xia, Ning-hong Song
Summary: The study found no difference in efficacy between elderly and young patients in most cancer types, except for melanoma patients receiving anti-PD-1 therapy. Elderly patients showed higher treatment response rate and more favorable prognosis in certain cancer types, potentially attributed to their high mutational properties. This suggests that modulating immune function could be beneficial to immunotherapy in elderly patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Karla M. Viramontes, Emily N. Neubert, Julia M. DeRogatis, Roberto Tinoco
Summary: PSGL-1 plays multiple regulatory roles in exhausted T cells, limiting their expansion in tumors and persistently infected hosts. It is also necessary for the long-term maintenance and optimal differentiation of exhausted T cells into specific subsets. Additionally, PSGL-1 restrains the reinvigoration potential of exhausted CD4(+) and CD8(+) T cells during ICI therapy. Targeting PSGL-1 may have therapeutic potential alone or in combination with other ICIs to reinvigorate exhausted T cells in patients with chronic infections or cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jingmei Pan, Xilin Li, Binfen Shao, Funeng Xu, Xuehui Huang, Xing Guo, Shaobing Zhou
Summary: A nanocarrier that achieves self-blockade of PD-L1 in tumor cells and a detection kit to quantitatively measure the binding rate of PD-1/PD-L1 have been developed, improving the efficacy of PD-1/PD-L1 self-blocking therapy.
ADVANCED MATERIALS
(2022)
Review
Biochemistry & Molecular Biology
Kenta Nakamura, Ryuhei Okuyama
Summary: Immune checkpoint inhibitors (ICIs) are used for the treatment of various cancers, and understanding the mechanism of tumor immune responses can improve their efficacy. Investigating T cell receptors (TCRs) and changes in the TCR repertoire has revealed increased proliferation of T cell clones in patients responding to ICIs. This proliferation is observed in tumors as well as in the peripheral blood, suggesting that analyzing immune cell repertoire can help predict and enhance the therapeutic efficacy of ICIs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sophie Rovers, Annelies Janssens, Jo Raskin, Patrick Pauwels, Jan P. van Meerbeeck, Evelien Smits, Elly Marcq
Summary: This review provides an overview of the current evidence of immune checkpoint inhibitors in malignant pleural mesothelioma (MPM) and discusses the potential of targeting TIGIT as a novel immunotherapy approach.
Article
Immunology
Sharif Rahmy, Sanket J. J. Mishra, Sean Murphy, Brian S. J. Blagg, Xin Lu
Summary: We developed a Hsp90 beta-selective inhibitor that is cytotoxic to cancer cells without inducing heat shock response. Our findings suggest that this Hsp90 beta inhibitor can significantly enhance the efficacy of ICB therapy and has good tolerability in mice.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
H. Atakan Ekiz, Christopher J. Conley, W. Zac Stephens, Ryan M. O'Connell
BMC BIOINFORMATICS
(2020)
Article
Microbiology
Diana Cortes-Selva, Lisa Gibbs, Andrew Ready, H. Atakan Ekiz, Ryan O'Connell, Bartek Rajwa, Keke C. Fairfax
Summary: Research has shown that offspring born to mothers infected with Schistosoma mansoni have immune defects in cellular immunity and IL-4 production during homeostasis and following vaccination. These defects may lead to long-term issues with cellular immune responses.
Article
Multidisciplinary Sciences
Thomas B. Huffaker, H. Atakan Ekiz, Cindy Barba, Soh-Hyun Lee, Marah C. Runtsch, Morgan C. Nelson, Kaylyn M. Bauer, William W. Tang, Timothy L. Mosbruger, James E. Cox, June L. Round, Warren P. Voth, Ryan M. O'Connell
Summary: This study highlights the role of IFN gamma and STAT1-inducible Nampt in shaping the metabolic program and function of tumor-associated macrophages. IFNy can polarize macrophages in the tumour microenvironment to an inflammatory state, impacting their anti-tumour function. The activation of NRE1, a regulatory region within the NAMPT gene, by IFNy-driven STAT1 plays a key role in regulating TAM functions.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Dennis K. Fix, H. Atakan Ekiz, Jonathan J. Petrocelli, Alec M. Mckenzie, Ziad S. Mahmassani, Ryan M. O'Connell, Micah J. Drummond
Summary: This study characterized macrophage metabolism and inflammation in aged muscle during early recovery from disuse atrophy using single cell transcriptomics and functional assays. The results indicate that aged bone marrow-derived pro-inflammatory macrophages display impaired glycolysis and phagocytosis function, potentially contributing to attenuated regrowth during muscle recovery.
Article
Oncology
Shu-Chin Alicia Lai, Harika Gundlapalli, H. Atakan Ekiz, Amanda Jiang, Elvelyn Fernandez, Alana L. Welm
Summary: Deletion of SF-Ron kinase enhances immune cell infiltration, boosts tumor-specific T cell responses, and eliminates breast cancer metastasis, suggesting potential for small-molecule Ron kinase inhibitors in metastatic breast cancer treatment.
Article
Cell Biology
W. Zac Stephens, Jason L. Kubinak, Arevik Ghazaryan, Kaylyn M. Bauer, Rickesha Bell, Kate Buhrke, Tyson R. Chiaro, Allison M. Weis, William W. Tang, Josh K. Monts, Ray Soto, H. Atakan Ekiz, Ryan M. O'Connell, June L. Round
Summary: Intestinal epithelial cells expressing MHC class II play a role in gut homeostasis and interact with immune cells to develop adaptive responses to microbial antigens within the gastrointestinal tract.
Article
Cardiac & Cardiovascular Systems
Wei Feng Ma, Adam W. Turner, Christina Gancayco, Doris Wong, Yipei Song, Jose Verdezoto Mosquera, Gaelle Auguste, Chani J. Hodonsky, Ajay Prabhakar, H. Atakan Ekiz, Sander W. van der Laan, Clint L. Miller
Summary: This article introduces PlaqView 2.0, an open-source web portal for exploring and analyzing cardiovascular single-cell datasets. PlaqView 2.0 offers enhanced features and functionalities, including additional cardiovascular single-cell datasets. It brings advanced tools and high-performance computing directly to users without the need for programming knowledge.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Immunology
William W. Tang, Kaylyn M. Bauer, Cindy Barba, Huseyin Atakan Ekiz, Ryan M. O'Connell
Summary: The rising toll of cancer globally necessitates ingenuity in early detection and therapy. In the last decade, the utilization of immune signatures and immune-based therapies has made significant progress in the clinic. Non-coding RNAs, specifically microRNAs, have been explored in pre-clinical contexts with tremendous success. MicroRNAs play indispensable roles in programming the interactions between immune and cancer cells, providing opportunities to complement and improve immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Meeting Abstract
Hematology
Ismail Can, Reona Leo Sakemura, Claudia Manriquez-Roman, Olivia Sirpilla, Carli M. Stewart, Kun Yun, Michelle J. Cox, Truc Huynh, James H. Girsch, Ekene J. Ogbodo, Lionel A. Kankeu Fonkoua, Mehrdad Hefazi, Michael W. Ruff, Justin C. Boysen, Elizabeth L. Siegler, Atakan Ekiz, Saad S. Kenderian, Neil E. Kay
Article
Immunology
Jacob W. Thompson, Ruozhen Hu, Thomas B. Huffaker, Andrew G. Ramstead, H. Atakan Ekiz, Kaylyn M. Bauer, William W. Tang, Arevik Ghazaryan, June L. Round, Robert S. Fujinami, Ryan M. OConnell
Summary: This study investigates the importance of miR-155 expression in distinct immune cell populations using single-cell RNA sequencing and cell-specific conditional miR-155 knockouts. The results show that miR-155 has distinct roles and requirements depending on the cell type, providing insights into the next generation of miRNA therapeutics.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Wan-Lin Lo, Miriam Kuhlmann, Gabrielle Rizzuto, H. Atakan Ekiz, Elizabeth M. Kolawole, Monica P. Revelo, Rakieb Andargachew, Zhongmei Li, Yuan-Li Tsai, Alexander Marson, Brian D. Evavold, Dietmar Zehn, Arthur Weiss
Summary: Mature T cells need to differentiate between brief interactions with self-peptides and prolonged binding to agonists. By accelerating the phosphorylation of LAT residue Y136, an adjacent Gly135Asp alteration disrupts ligand discrimination in vivo. LAT(G135D) T cells show excessive self-reactivity, leading to negative selection and T-cell anergy.
Article
Oncology
Cindy Barba, H. Atakan Ekiz, William Weihao Tang, Arevik Ghazaryan, Mason Hansen, Soh-Hyun Lee, Warren Peter Voth, Ryan Michael O'Connell
Summary: The tumor microenvironment comprises immune and tumor cells that interact with each other. Immune cells, through the release of inflammatory cytokines, such as interferons (IFNs), play a role in tumor clearance. However, it has been observed that tumor cells can also exploit IFNs to promote their growth and survival. This study demonstrates that interferon gamma (IFN gamma) induces the expression of NAMPT, an essential enzyme involved in the NAD+ salvage pathway, in melanoma cells. Increased NAMPT levels enhance cell proliferation and survival. Understanding the mechanisms underlying NAMPT regulation could lead to improved therapeutic strategies, particularly in immunotherapies utilizing IFN signaling.
Article
Cell Biology
Kate M. M. Warde, Lorenzo J. J. Smith, Lihua Liu, Chris J. J. Stubben, Brian K. K. Lohman, Parker W. W. Willett, Julia L. L. Ammer, Guadalupe Castaneda-Hernandez, Sikiru O. O. Imodoye, Chenge Zhang, Kara D. D. Jones, Kimber Converso-Baran, H. Atakan Ekiz, Marc Barry, Michael R. R. Clay, Katja Kiseljak-Vassiliades, Thomas J. J. Giordano, Gary D. D. Hammer, Kaitlin J. J. Basham
Summary: This study establishes a new model to investigate the influence of aging on cancer by studying age- and sex-dependent adrenal cancer. The researchers uncover a tumor-protective role for myeloid immune cells, which is enhanced by androgens.
Article
Oncology
Sandra D. Scherer, Alessandra Riggio, Fadi Haroun, Yoko S. DeRose, H. Atakan Ekiz, Maihi Fujita, Jennifer Toner, Ling Zhao, Zheqi Li, Steffi Oesterreich, Ahmed A. Samatar, Alana L. Welm
Summary: This study developed an immune-humanized PDX model for studying endocrine-resistant ER+ breast cancer, which contains a naturally occurring ESR1 mutation and recapitulates the lymphocyte-excluded and myeloid-rich tumor microenvironment of human ER+ breast tumors. The model provides a platform for studying mechanisms of endocrine resistance and tumor-immune interactions in a clinically relevant in vivo setting.
BREAST CANCER RESEARCH
(2021)
Meeting Abstract
Oncology
Shu-Chin Alicia Lai, Harika Gundlapalli, Huseyin A. Ekiz, Alana L. Welm