Article
Oncology
Lori D. Dwyer-Nield, Debbie G. McArthur, Tyler M. Hudish, Laura I. Hudish, Carol Mirita, Kayla Sompel, Alex J. Smith, Kiana Alavi, Moumita Ghosh, Daniel T. Merrick, Meredith A. Tennis, Robert L. Keith
Summary: Pioglitazone significantly reduces squamous lesions and the presence of airway basal cells in the NTCU mouse model. It also influences EMT gene expression to promote a more epithelial phenotype. These findings contribute to the understanding of PPAR gamma agonism as a chemoprevention strategy for lung cancer.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Ana Zulijani, Andrea Dekanic, Tomislav Cabov, Hrvoje Jakovac
Summary: The study evaluated the relationship and possible interactions between metallothioneins and megalin in different grades of oral squamous cell carcinoma and premalignant lesions, showing their co-expression and direct interaction in cancer tissue, indicating the oncogenic potential of the MTs-megalin interaction.
Article
Dentistry, Oral Surgery & Medicine
Shuang-Bo Xu, Meng-Yao Wang, Xin-Zhan Shi, Qiong Wang, Miao Yu, Wei Zhang, Xiao-Hui Xu, Lai-Kui Liu
Summary: The study found that PD-1 and PD-L1 may induce immune suppression in oral leukoplakia (OLK) and accelerate the progress of malignant transformation.
Article
Multidisciplinary Sciences
Sebastian Blatt, Maximilian Krueger, Constantin Rump, Stefanie Zimmer, Keyvan Sagheb, Julian Kuenzel
Summary: PD-L1 expression varies between oral and oropharyngeal squamous cell carcinoma, but does not affect patient survival. The status of p16 is also unrelated to PD-L1 expression.
Article
Biochemistry & Molecular Biology
Sonja Steen, Karl Semmelmayer, Christa Flechtenmacher, Juergen Hoffmann, Kolja Freier, Dominik Horn, Jochen Hess, Christian Freudlsperger, Julius Moratin
Summary: The introduction of immune checkpoint inhibition has provided a new treatment option for advanced oral cancers. However, there is a lack of data on the dynamic regulation of PD-L1 expression in recurrent tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Zhibin Liu, Yao Liu, Mingming Liu, Qingjia Gong, Anjie Shi, Xiuhong Li, Xu Bai, Xiaoyue Guan, Bing Hao, Feila Liu, Xing Zhou, Hongfeng Yuan
Summary: The PD-1/PD-L1 pathway may be involved in the pathogenesis of TAO by inhibiting T cell activity and regulating orbital fibroblast activation. Lack of PD-L1 in orbital fibroblasts may contribute to the active orbital inflammation in TAO patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
I-Tsang Chiang, Yuan-Hao Lee, Zhao-Lin Tan, Fei-Ting Hsu, Hsi-Feng Tu
Summary: Combination therapy with regorafenib and anti-PD-L1 can enhance anti-tumor immune response and suppress immunosuppression in oral squamous cell carcinoma (OSCC). This finding contributes to the development of more effective treatment strategies for OSCC.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Kit Kitichotkul, Nirush Lertprasertsuke, Sompid Kintarak, Surawut Pongsiriwet, Warit Powcharoen, Anak Iamaroon
Summary: This study investigated the expression of PD-L1 and its associations with HPV infection, p16 expression, and other clinical characteristics in patients with OSCC. The results showed that approximately one-fourth of OSCC patients were PD-L1-positive, and there was no association between HPV infection or p16 expression and PD-L1 expression.
Article
Biochemistry & Molecular Biology
Yutaro Kondo, Susumu Suzuki, Shoya Ono, Mitsuo Goto, Satoru Miyabe, Tetsuya Ogawa, Hiromi Tsuchida, Hideaki Ito, Taishi Takahara, Akira Satou, Toyonori Tsuzuki, Kazuhiro Yoshikawa, Ryuzo Ueda, Toru Nagao
Summary: The expression of PD-L1 is regulated by complex mechanisms. This study focused on the mechanisms of PD-L1 expression in OSCCs and found that EGF and IFN-gamma upregulate PD-L1 through different signaling pathways. Moreover, the phosphorylation pattern of related molecules in PD-L1-positive cells varied among different cases. These findings suggest that choosing the appropriate combination drugs for PD-1 blockade cancer treatment should consider the tissue environment and molecular alterations affecting PD-L1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Negar Khazan, Emily R. R. Quarato, Niloy A. A. Singh, Cameron W. A. Snyder, Taylor Moore, John P. P. Miller, Masato Yasui, Yuki Teramoto, Takuro Goto, Sabeeha Reshi, Jennifer Hong, Naixin Zhang, Diya Pandey, Priyanka Srivastava, Alexandra Morell, Hiroki Kawano, Yuko Kawano, Thomas Conley, Deepak M. M. Sahasrabudhe, Naohiro Yano, Hiroshi Miyamoto, Omar Aljitawi, Jane Liesveld, Michael W. W. Becker, Laura M. M. Calvi, Alexander S. S. Zhovmer, Erdem D. D. Tabdanov, Nikolay V. V. Dokholyan, David C. C. Linehan, Jeanne N. N. Hansen, Scott A. A. Gerber, Ashoke Sharon, Manoj K. K. Khera, Peter W. W. Jurutka, Natacha Rochel, Kyu Kwang Kim, Rachael B. B. Rowswell-Turner, Rakesh K. K. Singh, Richard G. G. Moore
Summary: The study identifies vitamin D/VDR as the driver of PD-L1 expression in AML and other cancers. They have developed a small molecule inhibitor called MeTC7 to target PD-L1 and inhibit tumorigenesis driven by PD-L1/PD-1. This provides a potential alternative to antibodies for controlling immune evasion in tumors.
Review
Oncology
Antian Gao, Xiao Pan, Xudong Yang, Zitong Lin
Summary: This review discusses the advantages of anti-PD-1/PD-L1 therapy for oral squamous cell carcinoma (OSCC) patients, and identifies three aspects currently available for predicting treatment efficacy.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Gastroenterology & Hepatology
Dror Kolodkin-Gal, Lior Roitman, Yossi Ovadya, Narmen Azazmeh, Benjamin Assouline, Yehuda Schlesinger, Rachel Kalifa, Shaul Horwitz, Yonatan Khalatnik, Anna Hochner-Ger, Ashraf Imam, Jonathan Abraham Demma, Eitan Winter, Hadar Benyamini, Sharona Elgavish, Areej A. S. Khatib, Karen Meir, Karine Atlan, Eli Pikarsky, Oren Parnas, Yuval Dor, Gideon Zamir, Ittai Ben-Porath, Valery Krizhanovsky
Summary: Cellular senescence limits tumourigenesis by blocking cell proliferation, but senescent cells can also promote tumour growth through paracrine effects. Senescent cells in early pancreatic lesions express a proinflammatory signature, and targeting these cells with the senolytic drug ABT-737 can reduce PanIN development and progression to pancreatic ductal adenocarcinoma. These findings suggest that eliminating senescent cells may be an effective preventive therapy for precancerous lesions.
Article
Medicine, Research & Experimental
Hunter Archibald, Krystina Kalland, Alexander Kuehne, Frank Ondrey, Brianne Roby, Luke Jakubowski
Summary: This study retrospectively analyzed the risk and incidence of head and neck cancer in Fanconi Anemia patients. The study found that 8.6% of patients in this population had leukoplakia or erythroplakia, and 3.8% developed malignancy. The study also suggested that screening for head and neck cancer should begin at age 10 or after hematopoietic stem cell transplant in Fanconi Anemia patients.
Article
Immunology
Tiantian Wu, Caijin Tang, Renchuan Tao, Xiangzhi Yong, Qiaozhi Jiang, Cong Feng
Summary: The research found that PD-L1 is highly expressed in oral squamous cell carcinoma (OSCC), correlated with worse survival, and related to macrophage infiltration and EMT process. Patients with high PD-L1 expression may benefit from ICI treatment and show higher sensitivity to certain chemical drugs.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Xiyang Tang, Jie Yang, Anping Shi, Yanlu Xiong, Miaomiao Wen, Zhonglin Luo, Huanhuan Tian, Kaifu Zheng, Yujian Liu, Chen Shu, Nan Ma, Rui Wang, Jinbo Zhao
Summary: CD155, a new immune checkpoint, is found to be highly expressed in esophageal squamous cell cancer (ESCA) and positively associated with PD-1/PD-L1 expression. It can support ESCA proliferation by regulating the cell cycle and inducing cell apoptosis through the PI3K/Akt and MAPK signaling pathways. Inhibition of CD155 may enhance the therapeutic effect of anti-PD-1 immunotherapies in ESCA.
Article
Oncology
Jessica M. Konen, B. Leticia Rodriguez, Aparna Padhye, Joshua K. Ochieng, Laura Gibson, Lixia Diao, Natalie W. Fowlkes, Jared J. Fradette, David H. Peng, Robert J. Cardnell, Jeffrey J. Kovacs, Jing Wang, Lauren A. Byers, Don L. Gibbons
Summary: The study demonstrates that a novel combination of MEK and AXL inhibitors effectively bypasses EMT-mediated drug resistance in KRAS/p53-mutant non-small cell lung cancer by targeting EMT subpopulations, thereby preventing tumor cell survival.
Article
Multidisciplinary Sciences
David H. Peng, B. Leticia Rodriguez, Lixia Diao, Pierre-Olivier Gaudreau, Aparna Padhye, Jessica M. Konen, Joshua K. Ochieng, Caleb A. Class, Jared J. Fradette, Laura Gibson, Limo Chen, Jing Wang, Lauren A. Byers, Don L. Gibbons
Summary: Understanding the resistance mechanisms in mutant KRAS lung cancers to targeted therapies and immune checkpoint blockade is crucial for developing novel combination therapies. MEK inhibition combined with anti-PD-L1 can synergistically reduce lung tumor growth, but resistance may develop eventually. Increased Th17 cell infiltration in resistant tumors promotes invasiveness and resistance to MEK inhibitors, and a triple therapy targeting MEK, PD-L1, and IL-17 may overcome this resistance for better in vivo responses.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Carla Calagua, Miriam Ficial, Caroline S. Jansen, Taghreed Hirz, Luke del Balzo, Scott Wilkinson, Ross Lake, Anson T. Ku, Olga Voznesensky, David B. Sykes, Philip J. Saylor, Huihui Ye, Sabina Signoretti, Haydn Kissick, Adam G. Sowalsky, Steven P. Balk, David J. Einstein
Summary: A subset of primary prostate cancer expresses PD-L1 and exhibits immunogenic characteristics. Immunogenic prostate cancer shows comparable CD8(+) T-cell content with renal cell carcinoma, potentially driven by genomic losses of RBI, BRCA2, and CHD1.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Siang-Boon Koh, Brian N. Dontchos, Veerle Bossuyt, Christine Edmonds, Simona Cristea, Nsan Melkonjan, Lindsey Mortensen, Annie Ma, Kassidy Beyerlin, Elyssa Denault, Elizabeth Niehoff, Taghreed Hirz, David B. Sykes, Franziska Michor, Michelle Specht, Constance Lehman, Leif W. Ellisen, Laura M. Spring
Summary: Systematic collection of fresh tissues for research during diagnostic breast biopsy is safe, feasible, and efficient, providing a high-yield mechanism for diverse interdisciplinary research. The study demonstrated high diagnostic concordance between research and clinical specimens, consistent cell recovery, and potential clinical relevance in analyzing HER2 levels and immune microenvironment diversity.
NPJ PRECISION ONCOLOGY
(2021)
Article
Oncology
Youmna Kfoury, Ninib Baryawno, Nicolas Severe, Shenglin Mei, Karin Gustafsson, Taghreed Hirz, Thomas Brouse, Elizabeth W. Scadden, Anna A. Igolkina, Konstantinos Kokkaliaris, Bryan D. Choi, Nikolas Barkas, Mark A. Randolph, John H. Shin, Philip J. Saylor, David T. Scadden, David B. Sykes, Peter Kharchenko
Summary: Bone metastases are devastating complications of cancer, particularly common in prostate cancer and refractory to immunotherapy. Analysis of single cells reveals multifaceted immune distortion in metastatic prostate cancer, with overexpression of CCL20 by myeloid cells and appearance of unique macrophages specific to PCa bone metastases. Disruption of the CCL20-CCR6 axis restores T cell reactivity and prolongs animal survival in mice with syngeneic PCa bone metastases, suggesting a targeted approach for relieving local immunosuppression.
Review
Respiratory System
Sara Tariq, So Yeon Kim, Jose Monteiro de Oliveira Novaes, Haiying Cheng
Summary: SCLC accounts for 14% of lung cancer cases and is highly aggressive with limited treatment options. Recent advances have identified potential therapeutic targets and subtypes, but further research is needed to improve treatment outcomes.
Review
Cell Biology
Rakhee Bajaj, Amanda N. Warner, Jared F. Fradette, Don L. Gibbons
Summary: The Golgi apparatus plays a crucial role in protein processing and trafficking in normal cells. Aberrant Golgi dynamics in cancer alter the tumor microenvironment and the immune landscape, enhancing the invasive and metastatic potential of cancer cells.
Article
Multidisciplinary Sciences
Adele M. Alchahin, Shenglin Mei, Ioanna Tsea, Taghreed Hirz, Youmna Kfoury, Douglas Dahl, Chin-Lee Wu, Alexander O. Subtelny, Shulin Wu, David T. Scadden, John H. Shin, Philip J. Saylor, David B. Sykes, Peter V. Kharchenko, Ninib Baryawno
Summary: By analyzing ccRCC patient samples using single-cell transcriptomics, a distinct transcriptional signature predictive of metastatic potential and patient survival was identified. Potential therapeutic targets including the CXCL9/CXCL10-CXCR3 axis and the CD70-CD27 axis were highlighted.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Samuel A. Kareff, Aliya Khan, Priscila Barreto-Coelho, Sunil Girish Iyer, Brian Pico, Michele Stanchina, Giselle Dutcher, Jose Monteiro de Oliveira Novaes, Aparna Nallagangula, Gilberto Lopes
Summary: This study retrospectively evaluated the impact of COVID-19 on cancer patients and providers in a community-facing cancer clinic. The results showed a significantly higher COVID-19 positivity rate among providers compared to patients, with almost two-thirds of patients experiencing treatment delays and 10% of cancer patients dying during the Omicron wave. The study highlights the continued threat of COVID-19 to cancer patients' treatment and livelihood, as well as the healthcare disparities faced by disadvantaged populations.
Article
Oncology
Kiranj Chaudagar, Hanna M. Hieromnimon, Rimpi Khurana, Brian Labadie, Taghreed Hirz, Shenglin Mei, Raisa Hasan, Jordan Shafran, Anne Kelley, Eva Apostolov, Ghamdan Al-Eryani, Kate Harvey, Srikrishnan Rameshbabu, Mayme Loyd, Kaela Bynoe, Catherine Drovetsky, Ani Solanki, Erica Markiewicz, Marta Zamora, Xiaobin Fan, Stephan Schuer, Alex Swarbrick, David B. Sykes, Akash Patnaik
Summary: This study aimed to elucidate the resistance mechanism to androgen deprivation therapy (ADT) and PI3K/AKT axis blockade in PTEN/p53-deficient metastatic castrate-resistant prostate cancer (mCRPC), and to develop rational combination strategies. The results showed that the combination of ADT and PI3Ki significantly enhanced anticancer responses by stimulating immune cell activation and reducing immune suppression of tumor-associated macrophages.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Mabel Perez-Oquendo, Roxsan Manshouri, Yanhua Tian, Jared J. Fradette, B. Leticia Rodriguez, Samrat T. Kundu, Don L. Gibbons
Summary: Epithelial-to-mesenchymal transition enables epithelial cells to acquire invasive capacity. The transcription repressor ZEB1 suppresses the expression of epithelial genes by binding to the E-boxes in gene promoter regions. Mass spectrometry analysis identified K811 acetylation as a novel posttranslational modification in ZEB1. Acetylation of ZEB1 promotes protein stability, interaction with other protein complexes, and the invasion/metastasis of lung adenocarcinoma through epithelial-to-mesenchymal transition.
MOLECULAR CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Taghreed Hirz, Shenglin Mei, Hirak Sarkar, Youmna Kfoury, Shulin Wu, Bronte M. Verhoeven, Alexander O. Subtelny, Dimitar V. Zlatev, Matthew W. Wszolek, Keyan Salari, Evan Murray, Fei Chen, Evan Z. Macosko, Chin-Lee Wu, David T. Scadden, Douglas M. Dahl, Ninib Baryawno, Philip J. Saylor, Peter V. Kharchenko, David B. Sykes
Summary: The treatment of low-risk primary prostate cancer only requires active surveillance, while high-risk disease necessitates multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and metastatic disease development remain clinical challenges due to immune escape and tumor progression mechanisms that are not well understood. Through single-cell RNA sequencing and spatial transcriptomic analyses, we comprehensively describe the tumor microenvironment in localized prostate cancer and its differences compared to adjacent normal samples and healthy controls. Our study reveals an immune suppressive tumor microenvironment characterized by suppressive myeloid populations, exhausted T-cells, and high stromal angiogenic activity. We also infer cell-to-cell relationships within undissociated tissue sections using ligand-receptor interaction measurements. Overall, our work provides a highly detailed and comprehensive resource on the prostate tumor microenvironment and tumor-stromal cell interactions.
NATURE COMMUNICATIONS
(2023)