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
Multidisciplinary Sciences
Gonzalo L. Gonzalez-Del Pino, Kunhua Li, Eunyoung Park, Anna M. Schmoker, Byung Hak Ha, Michael J. Eck
Summary: The dysregulation of the RAF/MEK/ERK pathway is associated with many cancers, making the proteins involved, like MEK, a focus of drug discovery efforts. Allosteric MEK inhibitors have complex effects on this pathway and are used in combination with BRAF inhibitors in malignant melanoma. Recent studies suggest that these inhibitors act most potently on BRAF/MEK complexes rather than on free active MEK.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Medicine, General & Internal
Ying Cheng, Hui Li, Liang Zhang, Jing-Jing Liu, Chang-Liang Yang, Shuang Zhang
Summary: In recent years, immune checkpoint inhibitors have made significant breakthroughs in the treatment of lung cancer, with combination immunotherapy being widely used to improve efficacy. The combination of PD-1/PD-L1 inhibitors with other treatment modalities is a current research focus.
CHINESE MEDICAL JOURNAL
(2021)
Article
Endocrinology & Metabolism
Yu Qin, Jennifer R. Wang, Ying Wang, Priyanka Iyer, Gilbert J. Cote, Naifa L. Busaidy, Ramona Dadu, Mark Zafereo, Michelle D. Williams, Renata Ferrarotto, G. Brandon Gunn, Peng Wei, Keyur Patel, Marie-Claude Hofmann, Maria E. Cabanillas
Summary: This study demonstrates the value of cfDNA gene mutation analysis in aiding early diagnosis and treatment selection for ATC patients. High concordance rates were observed between the mutations detected in cfDNA and those from tumor tissue sequencing. Patients with a PIK3CA mutation in cfDNA had worse overall survival, while BRAFi therapy significantly improved survival outcomes for ATC patients.
Review
Immunology
Quanqing Tang, Shihao Li, Gaozhen Huang, Hongwei Liu
Summary: Urothelial carcinoma (UC) is a common malignant tumor. Platinum-based chemotherapy has been the standard treatment for metastatic UC, but immune checkpoint inhibitors (ICIs) offer hope for patients unfit for platinum therapy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Rilan Bai, Jiuwei Cui
Summary: Antibodies targeting PD-1/PD-L1 have been considered breakthrough therapies for cancer. In addition to T cell-driven immune responses, blocking PD-1/PD-L1 may also enhance the function and activity of NK cells, which are often overlooked in previous studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Gang Liu, Xiaolan Lv, Yanling Ding, Yongbo Guo
Summary: This study aims to evaluate the efficacy and safety of PD1/PD-L1 inhibitor immunotherapy combined chemotherapy for inoperable advanced lung cancer through screening eligible studies and providing scientific evidence to guide clinical drug use.
Article
Pharmacology & Pharmacy
Shabnam Heydarzadeh, Ali Asghar Moshtaghie, Maryam Daneshpour, Mehdi Hedayati
Summary: This study investigates the potential of Apigenin, a plant derived flavonoid, in modulating tumor apoptosis by targeting GLUTs expression in anaplastic thyroid carcinoma. The results show that Apigenin treatment decreases the expression of GLUT1 and GLUT3 mRNA and protein levels in cancer cells, inhibiting cell migration and making them more susceptible to programmed cell death.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Oncology
Zaishang Li, Xueying Li, Wayne Lam, Yabing Cao, Hui Han, Xueqi Zhang, Jiequn Fang, Kefeng Xiao, Fangjian Zhou
Summary: Comparing anti-PD-1 and anti-PD-L1 therapies in platinum-resistant UC patients reveals that anti-PD-1 therapy exhibits better antitumor activity, with comparable safety profiles and survival outcomes. This systematic comparison may enhance treatment awareness in this patient population.
FRONTIERS IN ONCOLOGY
(2021)
Review
Medicine, Research & Experimental
Keywan Mortaezaee, Jamal Majidpoor
Summary: CD8+ T cells play a crucial role in combating cancer, but their infiltration and effector function are often impaired in cancer patients, leading to defective immunity and resistance to immunotherapy. The exclusion and exhaustion of CD8+ T cells are major factors contributing to the limited durability of immune checkpoint inhibitor therapy. Identifying and targeting factors responsible for defective CD8+ T cell infiltration and function could provide a promising supplementary approach in patients undergoing anti-PD-1/PD-L1 therapy. Recent development of bispecific antibodies against PD-(L)1 and key factors within the tumor microenvironment holds great potential in enhancing the effectiveness and safety of cancer immunotherapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Oncology
Ritsu Ibusuki, Yasuto Yoneshima, Mikiko Hashisako, Norikazu Matsuo, Taishi Harada, Yuko Tsuchiya-Kawano, Junji Kishimoto, Keiichi Ota, Yoshimasa Shiraishi, Eiji Iwama, Kentaro Tanaka, Yoshinao Oda, Isamu Okamoto
Summary: This study retrospectively evaluated the expression of TTF-1 in advanced non-squamous NSCLC patients treated with PD-1/PD-L1 inhibitors plus pemetrexed and platinum chemotherapy. It found that TTF-1-positive patients had longer progression-free survival (PFS) compared to TTF-1-negative patients.
TRANSLATIONAL LUNG CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Stefanie Hoyer, Valentina Eberlein, Gerold Schuler, Carola Berking, Lucie Heinzerling, Niels Schaft, Jan Doerrie
Summary: This study investigated the impact of BRAFi/MEKi on the maturation of monocyte-derived dendritic cells (moDCs) and their interaction with T cells. The findings showed that these inhibitors altered cytokine secretion and surface marker expression of DCs, leading to lower activation markers and cytokine secretion in T cells during antigen-specific stimulation。
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dermatology
Kazufumi Shirouchi, Sachiko Koshikawa, Koichiro Shinya, Hideaki Watanabe, Miki Izumi, Kiyoshi Yoshimura, Hirohiko Sueki
Summary: This study found that the expression of PD-1 and PD-L1 is decreased in patients with lichen planus, which may lead to increased infiltration of inflammatory cells targeting the epidermis. Further research is needed to elucidate the mechanism behind this phenomenon.
JOURNAL OF DERMATOLOGY
(2021)
Article
Oncology
Topias Karjula, Hanna Elomaa, Anne Niskakangas, Olli Mustonen, Iiris Puro, Teijo Kuopio, Maarit Ahtiainen, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Juha P. Vayrynen, Fredrik Yannopoulos, Olli Helminen
Summary: The study found that CD3(+) and CD8(+) T-cell density and PD-1/PD-L1 expression have prognostic value in pulmonary metastases of colorectal cancer. T-cell infiltration is higher in pulmonary metastases compared to primary tumors. High CD3(+) and CD8(+) cell density are associated with better survival, while high PD-L1 expression is associated with favorable prognosis.
Article
Biochemistry & Molecular Biology
Chihiro Tanaka, Takuro Kobori, Mayuka Tameishi, Yoko Urashima, Takuya Ito, Tokio Obata
Summary: The ERM family scaffold proteins play a role in PD-L1 expression in HeLa cells, with ezrin potentially acting as a scaffold protein for PD-L1 and regulating its protein expression. This finding suggests ezrin could be a therapeutic target for cervical cancer, improving immune checkpoint blockade therapy.
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
Medicine, Research & Experimental
Sarah C. Cowles, Allison Sheen, Luciano Santollani, Emi A. Lutz, Brianna M. Lax, Joseph R. Palmeri, Gordon J. Freeman, K. Dane Wittrup
Summary: Monoclonal antibodies targeting PD-1 show varied efficacy depending on their affinity, and a threshold affinity is required for maximum efficacy in the treatment of MC38 adenocarcinoma.
Article
Multidisciplinary Sciences
Vijayakumar Velu, Kehmia Titanji, Hasan Ahmed, Ravi Dyavar Shetty, Lakshmi S. Chennareddi, Gordon J. Freeman, Rafi Ahmed, Rama Rao Amara
Summary: The study demonstrated that PD-1 blockade following ART interruption significantly enhances the function of anti-viral CD8 T cells and improves viral control. It suggests the potential synergistic effects of PD-1 blockade with other immunotherapies inducing functional CD8 T-cell responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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)
