Review
Immunology
Hang Yin Chu, Zihao Chen, Luyao Wang, Zong-Kang Zhang, Xinhuan Tan, Shuangshuang Liu, Bao-Ting Zhang, Aiping Lu, Yuanyuan Yu, Ge Zhang
Summary: Wnt antagonist Dickkopf-1 (DKK1) is highly expressed in multiple cancers and associated with poor prognosis, promoting cancer growth and influencing immune cell activities, particularly MDSCs and CD8(+) T cells. DKK1 is considered a promising target for cancer immunotherapy, with ongoing research aimed at elucidating its functional mechanisms.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Xi-Yang Tang, Yan-Lu Xiong, Xian-Gui Shi, Ya-Bo Zhao, An-Ping Shi, Kai-Fu Zheng, Yu-Jian Liu, Tao Jiang, Nan Ma, Jin-Bo Zhao
Summary: Immunotherapy is a major treatment for tumors, but low response rate and high rates of immune-related adverse events are still problematic. This review focuses on IGSF11 and VISTA in tumors, examining their structure, expression, and functional regulation. IGSF11 and VISTA are highly expressed in tumors and participate in the regulation of immune cells and cytokine production. The downregulation of both inhibits tumor growth. Preclinical and clinical trials emphasize their predictive role in tumor prognosis. IGSF11 and VISTA have enormous potential in tumor immunotherapy.
BIOMARKER RESEARCH
(2022)
Review
Oncology
Lin-Lin Sun, Dong-Li Linghu, Mien-Chie Hung
Summary: Ferroptosis, a newly recognized type of programmed cell death, plays an important role in cancer biology and therapies. Certain tumors, such as TNBC, are particularly vulnerable to ferroptosis inducers. Recent studies suggest that ferroptosis is involved in T cell-mediated anti-tumor immunity.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Review
Oncology
Alyssa Min Jung Kim, Macy Rose Nemeth, Seung-Oe Lim
Summary: Immunotherapy has become an important therapeutic strategy for treating various diseases, including cancer. The 4-1BB receptor has shown promise as a therapeutic target in cancer immunotherapy and has garnered significant attention and research.
FRONTIERS IN ONCOLOGY
(2022)
Review
Immunology
Yu Hao, Xinxuan Zhou, Yiling Li, Bolei Li, Lei Cheng
Summary: Cluster of differentiation 47 (CD47) is a transmembrane protein that is widely present on cell surfaces and overexpressed by cancer cells. It interacts with signal-regulatory protein a (SIRPa) to inhibit macrophage-mediated phagocytosis and achieve immune escape. Targeting the CD47-SIRPa axis as a cancer immunotherapy has shown promising results in pre-clinical studies.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Yujing Zhang, Jihua Guo, Rong Jia
Summary: The maintenance of oral health has become a major global health challenge during the COVID-19 pandemic. Regulatory T cells (Treg) play essential roles in immune disorders associated with oral diseases, affecting the progression of periodontitis, apical periodontitis, oral precancerous lesions, and oral cancer. Understanding the distribution, function, and regulation of Treg cells may offer potential for immunotherapy in the treatment of oral diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Chu Xiao, Tao Fan, Yujia Zheng, He Tian, Ziqin Deng, Jingjing Liu, Chunxiang Li, Jie He
Summary: With the advancements in cancer immunity research, it has been discovered that histone modifications play a crucial role in establishing antitumor immunological ability. Combining epigenetic drugs with immune checkpoint blockades or chimeric antigen receptor-T cell therapies shows promise in improving immunotherapy outcomes. The specific histone modification, H3K4me3, is deeply involved in regulating tumor immunogenicity, reshaping tumor immune microenvironment, and regulating immune cell functions. However, there is still uncertainty in integrating these theoretical foundations and optimizing available therapies. This review explores the mechanisms by which H3K4me3 and its modifiers regulate antitumor immunity and discusses the potential of combining H3K4me3-related agents with immunotherapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Laura Schaekel, Salahuddin Mirza, Riekje Winzer, Vittoria Lopez, Riham Idris, Haneen Al-Hroub, Julie Pelletier, Jean Sevigny, Eva Tolosa, Christa E. Mueller
Summary: The study found that ceritinib, an anti-cancer drug, can also effectively inhibit CD39, providing a basis for the development of more potent CD39 inhibitors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Najibeh Shekari, Dariush Shanehbandi, Tohid Kazemi, Habib Zarredar, Behzad Baradaran, Seyed Amir Jalali
Summary: This article summarizes current evidence on V-domain immunoglobulin suppressor of T cell activation (VISTA), its related ligands, their interactions and effects, as well as preclinical and clinical targeting agents. Investigating VISTA ligands helps understand their functions and roles, and may facilitate the discovery of alternative therapeutic approaches targeting the VISTA pathway.
CANCER CELL INTERNATIONAL
(2023)
Review
Oncology
Ji-Eun Irene Yum, Young-Kwon Hong
Summary: VISTA is an emerging immune checkpoint molecule that plays a significant role in cancer progression by predominantly acting in an immune-suppressing manner. Ongoing clinical trials are investigating therapies targeting VISTA in various cancers.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Natalia Sauer, Natalia Janicka, Wojciech Szlasa, Bartlomiej Skinderowicz, Katarzyna Kolodzinska, Wioletta Dwernicka, Malgorzata Oslizlo, Julita Kulbacka, Vitalij Novickij, Katarzyna Karlowicz-Bodalska
Summary: The differential expression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in various tumor types has made it a trending topic. TIM-3 is a key immune checkpoint receptor that interacts with GAL-9, PtdSer, HMGB1, and CEACAM1. Its expression has been found in different immune cells and plays a crucial role in immunoregulation. Clinical trials incorporating TIM-3 targeting monoclonal and bispecific antibodies have shown promising results in enhancing anti-tumor effects and improving patient survival.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Immunology
Hai Zhao, Shuangshuang Song, Junwei Ma, Zhiyong Yan, Hongwei Xie, Ying Feng, Shusheng Che
Summary: CD47 is a protein that is ubiquitously expressed on the surface of cells and plays a critical role in self-recognition. It modulates cellular phagocytosis, determines the lifespan of erythrocytes, regulates immune cell activation, and manipulates synaptic pruning during neuronal development. Recently, CD47 has been identified as a novel target for cancer immunotherapy. This review discusses the diverse functions of CD47, its role in immune system homeostasis, and its potential therapeutic roles against cancer.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Jialiang Zheng, Fenglin Miao, Zhao Wang, Yuan Ma, Zhenhang Lin, Yaqin Chen, Xu Kong, Yue Wang, Aobo Zhuang, Ting Wu, Wengang Li
Summary: This study conducted a comprehensive analysis of the role of MDM2 in human cancer and found that MDM2 is a reliable prognostic biomarker closely related to cancer immunity, providing a potential immunotherapeutic target for breast cancer, bladder cancer, and ovarian cancer.
Review
Chemistry, Medicinal
Ya Zhang, Zelin Hu, Jifa Zhang, Changyu Ren, Yuxi Wang
Summary: This review summarizes the recent development of IDO1 dual-target inhibitors and focuses on the structure optimization process, structure-activity relationship, and the efficacy of in vitro and in vivo experiments. Dual-target inhibitors show great potential and advantages in addressing the challenges faced by IDO1 inhibitors in clinical trials.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Immunology
Xiaotian Song, Qianqian Si, Rui Qi, Weidan Liu, Miao Li, Mengyue Guo, Lin Wei, Zhiyan Yao
Summary: Tumorigenesis is a complex process involving various immunosuppressive mechanisms, with the degradation of tryptophan into kynurenine considered as a key mechanism. Among the enzymes involved in tryptophan metabolism, IDO1 stands out for its widespread distribution and high catalytic activity. Understanding the expression and biological function of IDO1 can offer insights into potential therapeutic strategies for malignant tumors targeting this enzyme.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zexian Zeng, Cheryl J. Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Shengqing Gu, Yi Zhang, Yang Liu, Xiaoqing Wang, Jingxin Fu, Liye Zhou, Boning Zhang, Sarah Kim, Kathleen B. Yates, Myles Brown, Gordon J. Freeman, Ravindra Uppaluri, Robert Manguso, X. Shirley Liu
Summary: Syngeneic mouse models derived from murine cancer cells engrafted on genetically identical mouse strains are valuable tools for studying tumor immunity and response to immunotherapy. Tumor Immune Syngeneic MOuse (TISMO) is a database with a wide collection of syngeneic mouse model profiles, providing interactive visualization features. TISMO includes both in vitro and in vivo RNA-seq samples from various cancer types and annotated sample metadata for research purposes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Qingyuan Huang, Fei Li, Hai Hu, Zhaoyuan Fang, Zhendong Gao, Guozhan Xia, Wai-Lung Ng, Alireza Khodadadi-Jamayran, Ting Chen, Jiehui Deng, Hua Zhang, Christina Almonte, Kristen Labbe, Han Han, Ke Geng, Sittinon Tang, Gordon J. Freeman, Yuan Li, Haiquan Chen, Kwok-Kin Wong
Summary: Mutations in TSC1 and TSC2 may affect antitumor immune response in lung cancer. The study found that TSC1/TSC2 knockout promotes PD-L1 expression and increases sensitivity to immune checkpoint blockade treatment.
Article
Oncology
Kathleen M. Mahoney, Petra Ross-Macdonald, Long Yuan, Linan Song, Eliseo Veras, Megan Wind-Rotolo, David F. McDermott, F. Stephen Hodi, Toni K. Choueiri, Gordon J. Freeman
Summary: This study investigated the levels of soluble PD-L1 (sPD-L1) before and during nivolumab treatment in metastatic clear cell renal cell carcinoma (RCC) and melanoma patients. The results showed that sPD-L1 levels were associated with worse prognosis and clinical factors. Additionally, changes in sPD-L1 levels during treatment were linked to treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
Wenjun Xiong, Xueliang Gao, Tiantian Zhang, Baishan Jiang, Ming-Ming Hu, Xia Bu, Yang Gao, Lin-Zhou Zhang, Bo-Lin Xiao, Chuan He, Yishuang Sun, Haiou Li, Jie Shi, Xiangling Xiao, Bolin Xiang, Conghua Xie, Gang Chen, Haojian Zhang, Wenyi Wei, Gordon J. Freeman, Hong-Bing Shu, Haizhen Wang, Jinfang Zhang
Summary: The study reveals how USP8 affects the efficacy of PD-1/PD-L1 immunotherapy by regulating PD-L1 protein abundance and activating the NF-kappa B signaling pathway, which in turn inhibits tumor growth by reshaping the tumor microenvironment and triggering immune responses.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Carlos R. Gil Del Alcazar, Anne Trinh, Alec Kovic, Ernesto Rojas Jimenez, Nicholas W. Harper, Michael U. J. Oliphant, Shanshan Xie, Ethan D. Krop, Bethlehem Lulseged, Katherine C. Murphy, Tanya E. Keenan, Eliezer M. Van Allen, Sara M. Tolaney, Gordon J. Freeman, Deborah A. Dillon, Senthil K. Muthuswamy, Kornelia Polyak
Summary: This study demonstrates the importance of a new breast cancer model for preclinical studies in cancer immunotherapy. The model accurately reproduces the molecular subtypes and immune characteristics of human breast cancer, and identifies markers of treatment response and resistance through gene expression profiling and spatial mapping. This provides a new research direction for immunotherapy in breast cancer.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Immunology
Stinne R. Greisen, Tue W. Kragstrup, Jesper Skovhus Thomsen, Kim Horslev-Pedersen, Merete Lund Hetland, Kristian Stengaard-Pedersen, Mikkel Ostergaard, Lykke Ornbjerg, Peter Junker, Arlene H. Sharpe, Gordon J. Freeman, Malene Hvid, Soren K. Moestrup, Ellen Margrethe Hauge, Bent Deleuran
Summary: The PD-1 pathway is closely associated with bone homeostasis, and lacking members of this pathway causes a deteriorated bone structure. In early rheumatoid arthritis patients, soluble PD-1 may serve as a biomarker, reflecting residual but clinically silent disease activity and radiographic progression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Yufei Wang, Alicia Buck, Marion Grimaud, Aedin C. Culhane, Sreekumar Kodangattil, Cecile Razimbaud, Dennis M. Bonal, Quang-De Nguyen, Zhu Zhu, Kevin Wei, Madison L. O'Donnell, Ying Huang, Sabina Signoretti, Toni K. Choueiri, Gordon J. Freeman, Quan Zhu, Wayne A. Marasco
Summary: Improving CAR-T cell therapy for solid tumors requires a better understanding of CAR design and cellular composition. A study found that CAR-T cells with a CD4/CD8 ratio of BB zeta exhibited superior efficacy in clearing clear-cell renal cell carcinoma (ccRCC) in a mouse model, demonstrating long-term tumor-free outcome.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Cell Biology
Ilaria Elia, Jared H. Rowe, Sheila Johnson, Shakchhi Joshi, Giulia Notarangelo, Kiran Kurmi, Sarah Weiss, Gordon J. Freeman, Arlene H. Sharpe, Marcia C. Haigis
Summary: This study reveals the mechanism by which tumor-derived lactate in the tumor microenvironment inhibits the cytotoxicity of CD8(+) T cells, highlighting the role of metabolic pathways in regulating T cell cytotoxicity.
Article
Multidisciplinary Sciences
James A. Torchia, Alexander H. Tavares, Laura S. Carstensen, Da -Yuan Chen, Jessie Huang, Tianshu Xiao, Sonia Mukherjee, Patrick M. Reeves, Hua Tu, Ann E. Sluder, Bing Chen, Darrell N. Kotton, Richard A. Bowen, Mohsan Saeed, Mark C. Poznansky, Gordon J. Freeman
Summary: As the SARS-CoV-2 virus evolves to evade natural antibodies, it also becomes less sensitive to therapeutic antibody drugs. However, an ACE2 decoy provides a neutralizing effect against antibody-resistant variants, including Omicron, without losing its potency. The inclusion of the ACE2 collectrin-like domain in the decoy not only improves its affinity for the viral S protein, but also unexpectedly prolongs its half-life in the blood and is necessary for reducing disease severity and viral replication in Syrian hamsters. The decoys' activity is attributed to their ability to trigger irreversible structural changes in the viral S protein.
Article
Oncology
Liya Ding, Qiwei Wang, Antons Martincuks, Michael J. Kearns, Tao Jiang, Ziying Lin, Xin Cheng, Changli Qian, Shaozhen Xie, Hye-Jung Kim, Inga-Maria Launonen, Anniina Faerkkilae, Thomas M. Roberts, Gordon J. Freeman, Joyce F. Liu, Panagiotis A. Konstantinopoulos, Ursula Matulonis, Hua Yu, Jean J. Zhao
Summary: This study reveals an adaptive immunosuppression mechanism that leads to resistance to PARP inhibition in BRCA1-mutant ovarian tumors. This resistance is mediated by an increased population of protumor tumor-associated macrophages (TAMs) and activation of the STAT3 signaling pathway. The use of STING agonists can reshape the immunosuppressive tumor microenvironment and overcome PARPi resistance in ovarian cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Multidisciplinary Sciences
Heng-Jia Liu, Heng Du, Damir Khabibullin, Mahsa Zarei, Kevin Wei, Gordon J. Freeman, David J. Kwiatkowski, Elizabeth P. Henske
Summary: This study reveals that B7-H3 expression is correlated with immunosuppressive phenotypes and worse clinical outcomes in human tumors with high mTORC1 activity. The authors show that mTORC1 upregulates B7-H3 expression by phosphorylating the transcription factor YY2. Inhibiting B7-H3 enhances T-cell activity and induces tumor cell expression of MHC-II, suppressing tumor growth with mTORC1 hyperactivity.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jing Liu, Xia Bu, Chen Chu, Xiaoming Dai, John M. Asara, Piotr Sicinski, Gordon J. Freeman, Wenyi Wei
Summary: The protein arginine methyltransferase PRMT1 suppresses the anti-tumor immune response by methylating cGAS and preventing its dimerization. Inhibition of PRMT1 activates the cGAS/STING-dependent DNA sensing signaling and increases the expression of interferon response genes, tumor-infiltrating lymphocytes, and tumoral PD-L1. Combination therapy of PRMT1 inhibitor with anti-PD-1 antibody enhances the anti-tumor therapeutic efficacy.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Atul Deshpande, Melanie Loth, Dimitrios N. Sidiropoulos, Shuming Zhang, Long Yuan, Alexander T. F. Bell, Qingfeng Zhu, Won Jin Ho, Cesar Santa-Maria, Daniele M. Gilkes, Stephen R. Williams, Cedric R. Uytingco, Jennifer Chew, Andrej Hartnett, Zachary W. Bent, Alexander V. Favorov, Aleksander S. Popel, Mark Yarchoan, Ashley Kiemen, Pei-Hsun Wu, Kohei Fujikura, Denis Wirtz, Laura D. Wood, Lei Zheng, Elizabeth M. Jaffee, Robert A. Anders, Ludmila Danilova, Genevieve Stein-O'Brien, Luciane T. Kagohara, Elana J. Fertig
Summary: Recent advances in spatial transcriptomics enable the measurement of gene expression in tissue samples while preserving their spatial context. This technology provides unprecedented resolution to study the regulatory pathways underlying heterogeneity in tumors and the tumor microenvironment. The bioinformatics algorithm SpaceMarkers allows for the inference of molecular changes from cell-cell interactions in spatial transcriptomics data and can identify location-specific molecular interactions within the tumor microenvironment.
Article
Medicine, Research & Experimental
Satomi Ando, Charles M. Perkins, Yamato Sajiki, Chase Chastain, Rajesh M. Valanparambil, Andreas Wieland, William H. Hudson, Masao Hashimoto, Suresh S. Ramalingam, Gordon J. Freeman, Rafi Ahmed, Koichi Araki
Summary: T cell exhaustion is associated with dysfunction and expression of PD-1. mTOR inhibition during the expansion phase enhances T cell response, while inhibition after exhaustion progresses causes immunosuppression with decreased TIM3(+) cells and increased viral load. mTOR signaling is essential for differentiation of stem-like T cells into TIM3(+) cells.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
