Article
Immunology
Zhen Xu, Hyo Shik Shin, Yoo Hyung Kim, Seong Yun Ha, Jae-Kyung Won, Su-jin Kim, Young Joo Park, Sareh Parangi, Sun Wook Cho, Kyu Eun Lee
Summary: This study aimed to establish a novel orthotopic ATC model in C57BL/6 mice and characterize the tumor microenvironment focusing immunity in the model. The results showed that compared with the B6129SF1 mouse model, this new model exhibited more aggressive tumor cell behaviors and strong immune responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Miguel A. Zaballos, Adrian Acuna-Ruiz, Marta Morante, Garcilaso Riesco-Eizaguirre, Piero Crespo, Pilar Santisteban
Summary: The study demonstrates that BRAF- and RAS-mutant thyroid cells respond differently to DEL-22379, which cannot be explained by the previously described mechanism of action of the inhibitor. Nonetheless, DEL-22379 exhibits significant anti-tumor effects against BRAF-mutant cells in vivo, while the anti-tumor effects are mild for RAS-mutant cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Endocrinology & Metabolism
Pia Adam, Stefan Kircher, Iuliu Sbiera, Viktoria Florentine Koehler, Elke Berg, Thomas Knoesel, Benjamin Sandner, Wiebke Kristin Fenske, Hendrik Blaeker, Constantin Smaxwil, Andreas Zielke, Bence Sipos, Stephanie Allelein, Matthias Schott, Christine Dierks, Christine Spitzweg, Martin Fassnacht, Matthias Kroiss
Summary: High tumoral expression of PD-L1 in a large proportion of ATCs and a subgroup of PDTCs provides a rationale for immune checkpoint inhibition. FGFR expression is generally low in thyroid tumor cells. No impact of PD-L1 and FGFR 1-4 expression was observed on disease specific survival. The clinically observed synergism of PEM with LEN may be caused by immune modulation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Sarika N. Rao, Robert C. Smallridge
Summary: Anaplastic thyroid cancer (ATC) is a highly malignant cancer with a low survival rate, especially in older women. It spreads rapidly to nearby structures and distant sites outside the neck. Despite the introduction of newer treatment strategies, further research is needed to improve survival outcomes.
BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Review
Oncology
Jiaqian Yuan, Yong Guo
Summary: Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive tumor that is resistant to traditional antitumor therapies. In recent years, targeted therapy has emerged as a promising treatment strategy, offering hope to patients with this malignant disease. This review summarizes the efficacy and adverse effects of various targeted drugs, providing valuable information for future research and clinical decision-making.
Article
Biochemistry & Molecular Biology
Cristina Pizzimenti, Vincenzo Fiorentino, Antonio Ieni, Esther Diana Rossi, Emanuela Germana, Luca Giovanella, Maria Lentini, Ylenia Alessi, Giovanni Tuccari, Alfredo Campenni, Maurizio Martini, Guido Fadda
Summary: The response to radioiodine therapy (RIT) in intermediate-risk differentiated thyroid cancer (DTC) patients is associated with BRAF mutations, AXL expression, and PD-L1 expression. These findings provide new biomarkers for personalized RIT in this patient population.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Mizuki Sekino, Manabu Iwadate, Yukie Yamaya, Yoshiko Matsumoto, Satoshi Suzuki, Hiroshi Mizunuma, Keiichi Nakano, Izumi Nakamura, Shinichi Suzuki
Summary: PD-L1 expression is associated with clinicopathological factors and prognosis in thyroid cancer, suggesting the potential efficacy of immune checkpoint inhibitors. This study aims to characterize PD-L1 expression, BRAF(V600E) mutation, and cellular and humoral immunity in thyroid cancer, and investigate predictors of anti-PD-L1 antibody therapy effectiveness. The findings suggest that PD-L1 expression is significantly correlated with BRAF(V600E) mutation and CD8+ expression, and can serve as a prognostic indicator for survival in patients with thyroid cancer.
Article
Biochemistry & Molecular Biology
Rena Pollack, Joshua Stokar, Natan Lishinsky, Irina Gurt, Naomi Kaisar-Iluz, Merav E. E. Shaul, Zvi G. G. Fridlender, Rivka Dresner-Pollak
Summary: Immune checkpoint inhibitors (ICI) commonly lead to adverse events in the thyroid, but the mechanism is not fully understood. Through RNA-sequencing, we found 952 differentially expressed genes (DEGs) in the thyroid tissues of a lung cancer murine model treated with αPD-1. Pathway analysis revealed that apoptosis and necrosis pathways were activated, leading to tissue destruction and thyroiditis. Our study suggests unique gene expression changes in the thyroid associated with αPD-1 therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Shimeng Zhou, Jinfeng Zhu, Jingwei Xu, Bingzi Gu, Qiao Zhao, Congzhou Luo, Zhoufeng Gao, Y. Eugene Chin, Xiaju Cheng
Summary: The PD-L1/PD-1 signaling pathway is considered one of the main mechanisms of tumor escape from immune surveillance. PD-L1 is highly expressed on tumor cells and binds to the PD-1 receptor on activated T cells, inhibiting their anti-tumor activity. Recent research has focused on post-translational modifications of PD-L1/PD-1, such as glycosylation, ubiquitination, phosphorylation, and acetylation, and their potential role in regulating the signaling pathway and anti-tumor function of T cells.
Review
Oncology
Ichiro Abe, Alfred King-yin Lam
Summary: Anaplastic thyroid carcinoma is a highly aggressive type of thyroid cancer, with common mutations in genes such as p53 and TERT. Current treatment options include curative resection, radiotherapy, and combination chemotherapies, with ongoing research on molecular targeted therapies and immunotherapy showing promise in managing this challenging cancer.
CURRENT ONCOLOGY REPORTS
(2021)
Review
Oncology
Jihane Boustani, Benoit Lecoester, Jeremy Baude, Charlene Latour, Olivier Adotevi, Celine Mirjolet, Gilles Truc
Summary: Combining radiation therapy with immune checkpoint inhibitors shows synergistic potential in enhancing anti-tumor immune responses, although optimization of treatment requires consideration of factors such as dose, fractionation, target volume, lymph nodes, and other immunomodulatory agents.
Article
Oncology
Maxwell J. Kroloff, Josefin-Beate Holz, Omer Stern, Christopher J. Shepherd, Michelle Morrow, Louis Kayitalire, Deborah J. Wong
Summary: This article presents a case of a patient with BRAF V600E-mutated, PD-L1 positive anaplastic thyroid cancer refractory to standard therapies, but achieving 3 years of disease control and partial response through treatment with FS118. Further investigation is needed to understand the mechanism of dual PD-L1/LAG-3 blockade by FS118 in overcoming initial PD-1 pathway resistance.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Chemistry, Multidisciplinary
Linfu Chen, Lin Zhang, Rui Zhao, Jingjing Shen, Yingyao Wang, Jiafei Zhu, Huapan Fang, Nanhui Liu, Cheng Wang, Ting Wei, Yu Chai, Maoyi Li, Chenghao Wu, Qian Chen, Zhuang Liu
Summary: This study presents a novel strategy for immunotherapy against colorectal tumors using orally administered anti-PD-L1 complexes. The complexes exhibited improved intestinal permeability and intertumoral penetration, and when combined with oxaliplatin chemotherapy, they inhibited tumor growth and prolonged animal survival. Oral administration achieved comparable therapeutic efficacy with reduced systemic immune-related adverse effects compared to systemic injection. This work provides a simple but effective approach for immunotherapy.
Article
Multidisciplinary Sciences
Huayun Yan, Yingfang Ma, Xinyue Zhou, Yushuang He, Yang Liu, Carlos Caulin, Leiming Wang, Heng Xu, Han Luo
Summary: Anaplastic thyroid cancer (ATC) is a rare and deadly malignancy with a poor prognosis and limited treatment options. However, research on its carcinogenesis, development, and therapy is hindered by low prevalence and difficulty in obtaining tissue samples. To address this, we created a genetically engineered ATC mouse model (mATC) that closely mimics the dynamics and immunological microenvironment of human ATC tumors. This model provides a valuable tool for studying the mechanisms and potential treatments for ATC.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Oncology
Xiaoming Wang, Yan Zhang, Jian Zheng, Cuixian Yao, Xiubo Lu
Summary: In anaplastic thyroid carcinoma, the lncRNA UCA1 attenuates the killing effect of cytotoxic CD8 + T cells on cancer cells through the miR-148a/PD-L1 pathway, providing insights into the potential mechanisms of immune evasion in this type of cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(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)
Correction
Immunology
Christopher S. Garris, Sean P. Arlauckas, Rainer H. Kohler, Marcel P. Trefny, Seth Garren, Cecile Piot, Camilla Engblom, Christina Pfirschke, Marie Siwicki, Jeremy Gungabeesoon, Gordon J. Freeman, Sarah E. Warren, SuFey Ong, Erica Browning, Christopher G. Twitty, Robert H. Pierce, Mai H. Le, Alain P. Algazi, Adil I. Daud, Sara I. Pai, Alfred Zippelius, Ralph Weissleder, Mikael J. Pittet
Article
Multidisciplinary Sciences
Masao Hashimoto, Koichi Araki, Maria A. Cardenas, Peng Li, Rohit R. Jadhav, Haydn T. Kissick, William H. Hudson, Donald J. McGuire, Rebecca C. Obeng, Andreas Wieland, Judong Lee, Daniel T. McManus, James L. Ross, Se Jin Im, Junghwa Lee, Jian-Xin Lin, Bin Hu, Erin E. West, Christopher D. Scharer, Gordon J. Freeman, Arlene H. Sharpe, Suresh S. Ramalingam, Alex Pellerin, Volker Teichgraber, William J. Greenleaf, Christian Klein, Jorg J. Goronzy, Pablo Umana, Warren J. Leonard, Kendall A. Smith, Rafi Ahmed
Summary: The study showed that combination therapy with PD-1 blockade and IL-2 during chronic lymphocytic choriomeningitis virus infection significantly alters the differentiation program of CD8(+) T cells, resulting in the generation of highly functional effector CD8(+) T cells that mediate viral control, thus providing a new perspective for cancer treatment.
Article
Medicine, General & Internal
Elsa Brunet-Ratnasingham, Antigoni Morou, Mathieu Dube, Julia Niessl, Amy E. Baxter, Olivier Tastet, Nathalie Brassard, Gloria Ortega-Delgado, Roxanne Charlebois, Gordon J. Freeman, Cecile Tremblay, Jean-Pierre Routy, Daniel E. Kaufmann
Summary: This study examined the expression and function of immune checkpoints in CD4+ T cells of HIV-infected individuals and found that the expression of immune checkpoints is associated with infection status and effector profile. In addition, different subsets of CD4+ T cells show varying sensitivity to PD-1-mediated inhibition, suggesting heterogeneity in the restoration of cell function through immune checkpoint blockade.
Meeting Abstract
Hematology
Elisa Ten Hacken, Gabriela Brunsting Hoffmann, Kayla Cruz, Erin Michelle Parry, Elizabeth Witten, Donna S. Neuberg, Gordon J. Freeman, Catherine J. Wu
Article
Immunology
Magdiel Perez-Cruz, Bettina P. Iliopoulou, Katie Hsu, Hsin-Hsu Wu, Tom Erkers, Kavya Swaminathan, Sai-Wen Tang, Cameron S. Bader, Neeraja Kambham, Bryan Xie, Rosemarie H. Dekruyff, Gordon J. Freeman, Everett Meyer
Summary: The study suggests that RGMb may play a role in the pathogenesis of GvHD and IBD. Treatment with an anti-RGMb monoclonal antibody in mouse models prevented GvHD and IBD, while maintaining the graft-versus-tumor effect. The findings highlight the potential of targeting RGMb as a therapeutic strategy for these conditions.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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)
Meeting Abstract
Immunology
Melissa Tian Bu, Long Yuan, Alyssa Klee, Gordon J. Freeman
JOURNAL OF IMMUNOLOGY
(2022)