Article
Oncology
Jeffrey R. White, Dakota T. Thompson, Kelsey E. Koch, Boris S. Kiriazov, Anna C. Beck, Dana M. van der Heide, Benjamin G. Grimm, Mikhail V. Kulak, Ronald J. Weigel
Summary: In melanoma metastasis, the role of the transcription factor AP-2 alpha is controversial, with some studies suggesting tumor suppressor activity while others show it facilitates metastasis by upregulating E2F pathway genes including EZH2. AP-2 alpha interacts with the NuRD complex, and its loss results in removal of activating chromatin marks and promotion of metastasis. These findings suggest AP-2 alpha can serve as a biomarker for predicting response to EZH2 inhibitors in treating advanced melanomas.
Article
Multidisciplinary Sciences
Shoubao Ma, Tingting Tang, Xiaojin Wu, Anthony G. Mansour, Ting Lu, Jianying Zhang, Li-Shu Wang, Michael A. Caligiuri, Jianhua Yu
Summary: PDGF-D mediates cell survival through the PDGFR beta signaling pathway without modulating effector functions of NK cells, providing new insights into the study of human NK cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Antonino A. A. Pane, Theresa Kordass, Agnes Hotz-Wagenblatt, Elke Dickes, Annette Kopp-Schneider, Rainer Will, Barbara Seliger, Wolfram Osen, Stefan B. B. Eichmueller
Summary: This study identified several miRNA species that can affect the susceptibility of melanoma cells to T cell-mediated killing. These miRNAs may represent attractive candidates for novel therapy approaches against melanoma and other tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Lenka Kyjacova, Rafael Saup, Kerstin Roensch, Sabine Wallbaum, Stefanie Dukowic-Schulze, Amelia Foss, Sandra D. Scherer, Melanie Rothley, Antje Neeb, Nicole Grau, Wilko Thiele, Sonja Thaler, Natascha Cremers, Carsten Sticht, Norbert Gretz, Boyan K. Garvalov, Jochen Utikal, Jonathan P. Sleeman
Summary: The sustained expression of IER2 drives melanoma invasion and progression through stimulating osteopontin secretion by inducing senescence in melanoma cells. Coordinate expression of IER2, p53/p21, and osteopontin in melanomas and metastases highlights the pathophysiological relevance of IER2-mediated senescence in melanoma progression.
Article
Biochemistry & Molecular Biology
Franziska Brauneck, Elisa Seubert, Jasmin Wellbrock, Julian Schulze zur Wiesch, Yinghui Duan, Tim Magnus, Carsten Bokemeyer, Friedrich Koch-Nolte, Stephan Menzel, Walter Fiedler
Summary: The study identified different NK cell subsets in AML patients, showing that CD56(dim)CD16(-) and CD56(bright)CD16(-) NK cells are predominant, with reduced CD56(dim)CD16(+) NK cells compared to healthy donors. TIGIT, PVRIG, CD39, and CD38 have different clustering patterns on these NK cell subsets and impact NK cell functionality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Young Shin Lee, Woong Heo, Ho-Jung Choi, Hae-Ryung Cho, Ji Ho Nam, Yong Gan Ki, Hong-Rae Lee, Woo-Chang Son, You-Soo Park, Chi-Dug Kang, Jaeho Bae
Summary: Ionizing radiation can increase the expression of PD-L1 in melanoma cells, suppress the activity of NK cells, and activate high levels of PD-1. PD-1/PD-L1 blockade might enhance immune responses of NK cells against melanoma cells after radiotherapy and overcome PD-L1 mediated radioresistance of cancer cells.
Article
Cell Biology
Ziqing Yang, Dandan Huang, Manqi Meng, Wencong Wang, Junyan Feng, Lekun Fang, Honglei Chen, Shaomin Zou
Summary: BAF53A is upregulated in colorectal cancer (CRC) and promotes CRC cell proliferation, colony formation, and tumorigenesis. Furthermore, BAF53A also participates in the development of CRC by regulating the DUSP5-ERK1/2 pathway.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Nancy D. Marin, Bradley A. Krasnick, Michelle Becker-Hapak, Leah Conant, Simon P. Goedegebuure, Melissa M. Berrien-Elliott, Keenan J. Robbins, Jennifer A. Foltz, Mark Foster, Pamela Wong, Celia C. Cubitt, Jennifer Tran, Christopher B. Wetzel, Miriam Jacobs, Alice Y. Zhou, David Russler-Germain, Lynne Marsala, Timothy Schappe, Ryan C. Fields, Todd A. Fehniger
Summary: The treatment of advanced melanoma is a clinical challenge, and natural killer (NK) cells show promise as a cellular therapy. Cytokine-induced memory-like (ML) differentiation enhances NK-cell responses against blood cancer targets, but its activity against solid tumors like melanoma needs further research. In preclinical studies, ML NK cells from healthy donors and melanoma patients exhibited increased IFN gamma production and cytotoxicity against melanoma targets, with a response partially dependent on activating receptors NKG2D and NKp46. Furthermore, in mouse models, ML NK cells showed better control of melanoma compared to conventional NK cells.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Gregory M. Kelly, Fares Al-Ejeh, Robert McCuaig, Francesco Casciello, Nabilah Ahmad Kamal, Blake Ferguson, Antonia L. Pritchard, Sayed Ali, Ines P. Silva, James S. Wilmott, Georgina Long, Richard A. Scolyer, Sudha Rao, Nicholas K. Hayward, Frank Gannon, Jason S. Lee
Summary: The study suggests that LC3B may serve as a biomarker for checkpoint inhibitor blockade to guide patient selection. Additionally, G9a inhibition shows potential in enhancing the efficacy of checkpoint inhibitor blockade and increasing response rates in melanoma patients undergoing immunotherapy.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Matsuda, Fumihiko Nishimura, Mitsutoshi Nakamura, Shuichi Yamada, Ichiro Nakagawa, Young-Soo Park, Takahiro Tsujimura, Hiroyuki Nakase
Summary: Studies have shown that enhancing NK cell-mediated cytotoxicity on GBM cells through TIM3 knockout using CRISPR-Cas9 technology may be a promising immunotherapeutic alternative.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Laura Kiekens, Sigrid Wahlen, Eva Persyn, Zenzi De Vos, Tom Taghon, Bart Vandekerckhove, Georges Leclercq
Summary: The study demonstrates that human ILC3s can convert into functional NK cells, with T-BET being the main driver.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Charles Q. Yang, Huan Wang, Zhenqiu Liu, Matthew T. Hueman, Aadya Bhaskaran, Donald E. Henson, Li Sheng, Dechang Chen
Summary: This study introduces machine learning as a novel tool to integrate additional prognostic factors into the TNM staging system for more accurate risk classification and survival prediction in patients with cutaneous melanoma. By utilizing the Ensemble Algorithm for Clustering Cancer Data (EACCD), a more advanced prognostic system was developed that improved patient stratification and survival prediction accuracy. The integration of additional factors separated favorable from unfavorable clinical outcomes, enhancing cohort selection for clinical trials and treatment management.
Article
Virology
Amanda B. Macedo, Callie Levinger, Bryan N. Nguyen, Jonathan Richard, Mamta Gupta, Conrad Russell Y. Cruz, Andres Finzi, Katherine B. Chiappinelli, Keith A. Crandall, Alberto Bosque
Summary: In this study, we found that HODHBt enhances IL-15 signaling in natural killer cells, leading to increased cytotoxicity and memory-like functions. This suggests that pharmacological enhancement of IL-15-mediated STAT activation could be a new approach for HIV treatment.
JOURNAL OF VIROLOGY
(2022)
Article
Medicine, Research & Experimental
Jane H. C. Loong, Tin-Lok Wong, Man Tong, Rakesh Sharma, Lei Zhou, Kai-Yu Ng, Hua-Jian Yu, Chi-Han Li, Kwa Man, Chung-Mau Lo, Xin-Yuan Guan, Terence K. Lee, Jing-Ping Yun, Stephanie K. Y. Ma
Summary: Glucose restriction promotes cancer stemness by inducing fucosylation, driving drug resistance and tumor recurrence. Inhibiting FUT1 can mitigate tumor growth and drug resistance, and enhance sensitivity to sorafenib in hepatocellular carcinoma patients.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Filip Tichanek, Asta Foersti, Akseli Hemminki, Otto Hemminki, Kari Hemminki
Summary: This study analysed the survival rates of melanoma in Denmark, Finland, Norway, and Sweden from 1971 to 2020. The results showed a significant increase in survival rates over the past few decades, which could be attributed to the population's awareness of sun protection and early detection, as well as the use of novel targeted therapies and immunotherapy.
EUROPEAN JOURNAL OF CANCER
(2023)
Letter
Oncology
Dirk Schadendorf
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Jeffrey S. Weber, Dirk Schadendorf, Michele Del Vecchio, James Larkin, Victoria Atkinson, Michael Schenker, Jacopo Pigozzo, Helen Gogas, Stephane Dalle, Nicolas Meyer, Paolo A. Ascierto, Shahneen Sandhu, Thomas Eigentler, Ralf Gutzmer, Jessica C. Hassel, Caroline Robert, Matteo S. Carlino, Anna Maria Di Giacomo, Marcus O. Butler, Eva Munoz-Couselo, Michael P. Brown, Piotr Rutkowski, Andrew Haydon, Jean-Jacques Grob, Jacob Schachter, Paola Queirolo, Luis de la Cruz-Merino, Andrew Haydon, Jean-Jacques Grob, Jacob Schachter, Paola Queirolo, Luis De La Cruz-Merino, Andre van der Westhuizen, Alexander M. Menzies, Sandra Re, Tuba Bas, Veerle de Pril, Julia Braverman, Daniel J. Tenney, Hao Tang, Georgina Long
Summary: The CheckMate 915 trial compared adjuvant nivolumab plus ipilimumab with nivolumab alone in patients with resected melanoma. The study found that there was no significant difference in recurrence-free survival between the two treatment groups.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Microbiology
Philipp Jansen, Adelaida Creosteanu, Viktor Matyas, Amrei Dilling, Ana Pina, Andrea Saggini, Tobias Schimming, Jennifer Landsberg, Birte Burgdorf, Sylvia Giaquinta, Hansgeorg Mueller, Michael Emberger, Christian Rose, Lutz Schmitz, Cyrill Geraud, Dirk Schadendorf, Joerg Schaller, Maximilian Alber, Frederick Klauschen, Klaus G. Griewank
Summary: In this study, a machine learning algorithm was used to detect fungal elements on digitized histologic sections of human nail specimens, and its performance was compared with that of dermatopathologists. The results demonstrated that the algorithm achieved a comparable sensitivity to the human pathologists. This finding suggests that machine learning algorithms can serve as supportive diagnostic tools to improve the screening efficiency of fungal infections.
Article
Oncology
Lucas Schneider, Christoph Wies, Eva I. Krieghoff-Henning, Tabea-Clara Bucher, Jochen S. Utikal, Dirk Schadendorf, Titus J. Brinker
Summary: In this study, the contribution of different data types in a combined classifier for predicting BRAF mutation status in melanoma was analyzed. The multimodal classifier showed improved generalisability compared to individual classifiers.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Alexander C. J. van Akkooi, Dirk Schadendorf, Alexander M. M. Eggermont
Summary: Sentinel lymph node biopsy (SLNB) was introduced in the 1990s to identify patients who may benefit from completion lymph node dissection. SLNB staging has been found to be the best for staging melanoma. Adjuvant systemic therapy and biomarkers are emerging, which might reduce the need for SLNB staging in the future.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Dermatology
Jan-Malte Placke, Delphine Mertens, Alpaslan Tasdogan, Eleftheria Chorti, Dirk Schadendorf, Selma Ugurel, Alexander Roesch, Ingo Stoffels, Joachim Klode
Summary: This study demonstrates that multispectral optoacoustic tomography (MSOT) can differentiate between benign and malignant lymphadenopathy by measuring the levels of oxyhemoglobin and deoxyhemoglobin in lymph nodes. It offers a noninvasive approach to avoid unnecessary lymph node biopsies and surgeries.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2023)
Article
Infectious Diseases
Laven Mavarani, Sarah Albayrak-Rena, Anja Potthoff, Martin Hower, Sebastian Dolff, Stefanie Sammet, Felix Maischack, Dirk Schadendorf, Boerge Schmidt, Stefan Esser
Summary: Our study evaluated the changes in weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) over a 5-year follow-up in people living with HIV (PLH) compared to the general population. The results showed that PLH had greater increases in weight and BMI after 5 years, but lower WHR change compared to the general population.
Article
Oncology
Filippo de Braud, Christophe Dooms, Rebecca S. Heist, Celeste Lebbe, Martin Wermke, Anas Gazzah, Dirk Schadendorf, Piotr Rutkowski, Juergen Wolf, Paolo A. Ascierto, Ignacio Gil-Bazo, Shumei Kato, Maria Wolodarski, Meredith McKean, Eva Munoz Couselo, Martin Sebastian, Armando Santoro, Vesselina Cooke, Luca Manganelli, Kitty Wan, Anil Gaur, Jaeyeon Kim, Giordano Caponigro, Xuan-Mai Couillebault, Helen Evans, Catarina D. Campbell, Sumit Basu, Michele Moschetta, Adil Daud
Summary: This study explores a targeted therapy for treating NRAS-mutant melanoma, showing promising antitumor activity in patients with the use of LXH254 and trametinib in combination.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Paolo Antonio Ascierto, Evan J. Lipson, Reinhard Dummer, James Larkin, Georgina V. Long, Rachel E. Sanborn, Vanna Chiarion-Sileni, Brigitte Dreno, Stephane Dalle, Dirk Schadendorf, Margaret K. Callahan, Marta Nyakas, Victoria Atkinson, Carlos Alberto Gomez-Roca, Naoya Yamazaki, Hussein A. Tawbi, Naomey Sarkis, Deepti Warad, Sonia Dolfi, Priyam Mitra, Satyendra Suryawanshi, Jean-Jacques Grob
Summary: Preliminary research shows that nivolumab and relatlimab have better efficacy in treating advanced melanoma patients who have previously received anti-PD-(L)1 treatment. The RELATIVITY-047 trial demonstrated that nivolumab and relatlimab, compared to nivolumab alone, significantly improved progression-free survival in previously untreated advanced melanoma patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Dirk Schadendorf, Hussein Tawbi, Evan J. Lipson, F. Stephen Hodi, Piotr Rutkowski, Helen Gogas, Christopher D. Lao, Jean-Jacques Grob, Andriy Moshyk, Jennifer Lord-Bessen, Melissa Hamilton, Shien Guo, Ling Shi, Sarah Keidel, Georgina Long
Summary: The RELATIVITY-047 trial demonstrates that the fixed-dose combination of nivolumab plus relatlimab improves progression-free survival in patients with advanced melanoma while maintaining stable health-related quality of life. Although the combination treatment is associated with a higher incidence of severe adverse events, patients' discomfort with these events is low, supporting NIVO + RELA as a first-line treatment option.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Philipp Jansen, Daniel Otero Baguer, Nicole Duschner, Jean Le'Clerc Arrastia, Maximilian Schmidt, Jennifer Landsberg, Joerg Wenzel, Dirk Schadendorf, Eva Hadaschik, Peter Maass, Joerg Schaller, Klaus Georg Griewank
Summary: In this study, a deep learning method was used to analyze histological tissue sections of melanoma patients, enabling accurate detection of lymph node metastasis and providing valuable reference for pathologists. The method was able to identify the size and classify the tumor, which is of great significance for prognosis assessment and treatment planning.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Carola Berking, Elisabeth Livingstone, Dirk Debus, Carmen Loquai, Michael Weichenthal, Ulrike Leiter, Felix Kiecker, Peter Mohr, Thomas K. Eigentler, Janina Remy, Katharina Schober, Markus V. Heppt, Imke von Wasielewski, Dirk Schadendorf, Ralf Gutzmer
Summary: The outcome of advanced melanoma patients has greatly improved over the past 15 years. Targeted therapies blocking BRAF or inhibiting immune checkpoints have shown significant efficacy in improving overall survival. The COMBI-r study confirms the efficacy of dabrafenib plus trametinib in routine clinical practice and provides additional data in patients with brain metastases or previous treatments.
Article
Oncology
Esmee P. Hoefsmit, Franziska Vollmy, Elisa A. Rozeman, Irene L. M. Reijers, Judith M. Versluis, Liesbeth Hoekman, Alexander C. J. van Akkooi, Georgina Long, Dirk Schadendorf, Reinhard Dummer, Maarten Altelaar, Christian U. Blank
Summary: Taking into account the higher response rates of neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma compared to stage IV disease, researchers hypothesized that systemic immune suppression may be responsible for lower response rates and disease recurrence. Through proteomic profiling, they found that the protein LRG1 is associated with worse prognosis and can serve as a biomarker for identifying high-risk patients and as a potential target for neoadjuvant ICB therapy.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Philipp Jansen, Jean Le 'Clerc Arrastia, Daniel Otero Baguer, Maximilian Schmidt, Jennifer Landsberg, Joerg Wenzel, Michael Emberger, Dirk Schadendorf, Eva Hadaschik, Peter Maass, Klaus Georg Griewank
Summary: This study highlights the enormous potential of artificial intelligence in pathology, showing that it can aid in the identification of rare cutaneous adnexal tumors and potentially become a standard tool in routine diagnostics.
EUROPEAN JOURNAL OF CANCER
(2024)
Article
Oncology
Paolo A. Ascierto, Reinhard Dummer, Helen J. Gogas, Ana Arance, Mario Mandala, Gabriella Liszkay, Claus Garbe, Dirk Schadendorf, Ivana Krajsova, Ralf Gutzmer, Vanna Chiarion-Sileni, Caroline Dutriaux, Jan Willem B. de Groot, Naoya Yamazaki, Carmen Loquai, Caroline Robert, Keith T. Flaherty
Summary: The purpose of this study was to evaluate the efficacy and safety of encorafenib alone or in combination with binimetinib for the treatment of advanced BRAF(V600)-mutant melanoma. The results showed that the combination of encorafenib and binimetinib improved progression-free survival and overall response rate, and had better tolerability compared to encorafenib alone.
JOURNAL OF CLINICAL ONCOLOGY
(2023)