Review
Immunology
Siqing Jiang, Xin Li, Lihua Huang, Zhensheng Xu, Jinguan Lin
Summary: Head and neck cancer is highly heterogeneous with poor prognosis. Prognostic markers such as PD-1, PD-L1, and PD-L2 have been studied, but their value is still debated. This article summarizes the different prognostic values of these markers in head and neck cancer based on cell types, tissue localization, and protein forms. It suggests the need for further research and the development of new evaluation systems.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pathology
Valentina B. Stevenson, Samantha N. Perry, Michelle Todd, William R. Huckle, Tanya LeRoith
Summary: In both canine and human melanoma, overexpression of the PD-1/PD-L1/PD-L2 axis is a common feature. High levels of PD-1 and PD-L1 are associated with increased numbers of CD3(+) cells.
VETERINARY PATHOLOGY
(2021)
Review
Pharmacology & Pharmacy
Yuqian Feng, Huimin Jin, Kaibo Guo, Yuying Xiang, Yiting Zhang, Wurong Du, Minhe Shen, Shanming Ruan
Summary: The study supports the efficacy of combination therapy with immune checkpoint inhibitors (ICIs) in cancer treatment, especially showing longer PFS in patients with high PD-L1 expression. More high-quality clinical randomized controlled trials are needed in the future to confirm these findings, as the number of included trials was limited.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Hao Zhang, Ziyu Dai, Wantao Wu, Zeyu Wang, Nan Zhang, Liyang Zhang, Wen-Jing Zeng, Zhixiong Liu, Quan Cheng
Summary: The regulatory mechanisms of PD-L1 and CTLA-4 play a crucial role in immunotherapy, and understanding their interactions can help improve patients' treatment responses and clinical care.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Daniele Borsetto, Michele Tomasoni, Karl Payne, Jerry Polesel, Alberto Deganello, Paolo Bossi, James R. Tysome, Liam Masterson, Giancarlo Tirelli, Margherita Tofanelli, Paolo Boscolo-Rizzo
Summary: This study provides evidence for the prognostic significance of CD8+ and CD4+ TILs in HNSCC, with variations in tumor subsite needing further investigation. TILs may serve as predictive biomarkers for risk stratifying patients and further research is needed in the application of immune-checkpoint inhibitors.
Article
Oncology
Behrus Puladi, Mark Ooms, Svetlana Kintsler, Khosrow Siamak Houschyar, Florian Steib, Ali Modabber, Frank Hoelzle, Ruth Knuechel-Clarke, Till Braunschweig
Summary: This study aimed to achieve reproducible and reliable PD-L1 scoring using artificial intelligence to enhance patient selection for checkpoint inhibitors. Results showed comparable performance between human-human and human-machine interactions, providing deeper insights into the function and limitations of automated scoring by artificial intelligence.
Review
Oncology
Liming Liao, Huilin Xu, Yuhan Zhao, Xiaofeng Zheng
Summary: Immunotherapies based on immune checkpoint blockade have improved cancer therapy outcomes in the past decade. However, some patients show poor responsiveness to this therapy, and the underlying mechanism is not well understood. Recent studies have shown that targeting tumor metabolism in combination with immune checkpoint inhibitors provides new approaches to cancer therapy.
FRONTIERS OF MEDICINE
(2023)
Review
Medicine, Research & Experimental
Parisa Shiri Aghbash, Narges Eslami, Ali Shamekh, Taher Entezari-Maleki, Hossein Bannazadeh Baghi
Summary: The COVID-19 pandemic, caused by the outbreak of SARS-CoV-2 in Wuhan in December 2019, highlights the significance of respiratory disorders, lymphopenia, cytokine cascades, and immune responses in disease severity. Investigation of inhibitory immune checkpoints could impact treatment strategies, with T-cells playing a key role in clearing viral infections and reducing symptoms. Lymphocyte depletion and enhanced expression of inhibitory immune checkpoints in individuals with COVID-19 contribute to T-cell dysfunction and exhaustion, particularly in severe cases.
Review
Immunology
Andrea Botticelli, Alessio Cirillo, Lidia Strigari, Filippo Valentini, Bruna Cerbelli, Simone Scagnoli, Edoardo Cerbelli, Ilaria Grazia Zizzari, Carlo Della Rocca, Giulia D'Amati, Antonella Polimeni, Marianna Nuti, Marco Carlo Merlano, Silvia Mezi, Paolo Marchetti
Summary: This study compared the efficacy of anti-PD-1 and anti-PD-L1-based therapy in R/M HNSCC patients through a systematic review and network meta-analysis. It found no significant differences in overall survival between different subgroups, except for metastatic patients where anti-PD-1-based therapy was associated with significantly less risk of death.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Hikmat H. Assi, Chihunt Wong, Kimberly A. Tipton, Li Mei, Ken Wong, Jennifer Razo, Chanty Chan, Bruce Howng, Jason Sagert, Michael Krimm, Linnea Diep, Andrew Jang, Margaret T. Nguyen, Nicole Lapuyade, Victoria Singson, Ruth Villanueva, Madan Paidhungat, Shouchun Liu, Vangipuram Rangan, Olga Vasiljeva, James W. West, Jennifer H. Richardson, Bryan Irving, Dylan Daniel, Marcia Belvin, W. Michael Kavanaugh
Summary: Using protease-activatable antibody prodrugs (Pb-Tx) to locally inhibit PD-1/PD-L1 can reduce systemic immune toxicity while eliciting potent anti-tumor immune responses.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Agriculture, Dairy & Animal Science
Ilaria Porcellato, Samanta Mecocci, Chiara Brachelente, Katia Cappelli, Federico Armando, Alessia Tognoloni, Elisabetta Chiaradia, Valentina Stefanetti, Luca Mechelli, Marco Pepe, Rodolfo Gialletti, Benedetta Passeri, Alessandro Ghelardi, Elisabetta Razzuoli
Summary: The study investigated the expression of PD-L1 and CTLA-4 in penile tumors of horses, particularly in malignant squamous cell carcinomas. Results showed that these molecules are not frequently expressed in equine penile tumors, suggesting limited efficacy of ICI in treating these tumors.
Article
Radiology, Nuclear Medicine & Medical Imaging
Hans-Jonas Meyer, Anne Kathrin Hohn, Alexey Surov
Summary: This study used DWI to investigate the relationship between tumor-infiltrating lymphocytes, tumor-stroma ratio, and vimentin expression in HNSCC. The results showed that ADC skewness and kurtosis histogram parameters can reflect tumor compartments in HNSCC. ADC entropy was significantly associated with TIL within the tumor compartment.
ACADEMIC RADIOLOGY
(2022)
Article
Oncology
Satoshi Muto, Sho Inomata, Hikaru Yamaguchi, Hayato Mine, Hironori Takagi, Yuki Ozaki, Masayuki Watanabe, Takuya Inoue, Takumi Yamaura, Mitsuro Fukuhara, Naoyuki Okabe, Yuki Matsumura, Takeo Hasegawa, Jun Osugi, Mika Hoshino, Mitsunori Higuchi, Yutaka Shio, Hiroyuki Suzuki
Summary: The proportions of CTLA-4(+) regulatory T cells to CD8 T cells and CTLA-4(+) cells in CD8 T cells were found to be irrelevant to the PD-L1 TPS in NSCLC patients.
ANTICANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Murat Tekguc, James Badger Wing, Motonao Osaki, Jia Long, Shimon Sakaguchi
Summary: Regulatory T cells reduce the expression of CD80/CD86 on antigen-presenting cells through CTLA-4-dependent trogocytosis, inhibiting T cell immune responses. This mechanism can have dual suppressive effects, limiting CD80/CD86 costimulation to naive T cells and increasing free PD-L1 available for the inhibition of PD-1-expressing effector T cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Pharmacology & Pharmacy
Ze Xiang, Jiayuan Li, Zhengyu Zhang, Chao Cen, Wei Chen, Bin Jiang, Yiling Meng, Ying Wang, Bjoern Berglund, Guanghua Zhai, Jian Wu
Summary: Immunotherapy with immune checkpoint inhibitor (ICI) drugs is a hot topic in cancer treatment. Our study used Bayesian model to comprehensively evaluate the safety and efficacy of ICI drugs. Different ICI drug therapies may have different risks in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Treatment with cemiplimab was found to be the best choice in terms of PFS and OS. Our study provides new insights and strategies for the clinical practice of ICI drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Otorhinolaryngology
Angela Horvath, Peter Prekopp, Gabor Polony, Eszter Szekely, Laszlo Tamas, Kornel Danos
Summary: This study evaluated the accuracy of detecting lymph node metastases in head and neck cancer patients, finding that both conventional imaging modalities and fine-needle aspiration cytology had relatively low sensitivity and could not definitively exclude the presence of regional tumor metastasis.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2021)
Article
Oncology
Torsten O. Nielsen, Samuel C. Y. Leung, David L. Rimm, Andrew Dodson, Balazs Acs, Sunil Badve, Carsten Denkert, Matthew J. Ellis, Susan Fineberg, Margaret Flowers, Hans H. Kreipe, Anne-Vibeke Laenkholm, Hongchao Pan, Friderique M. Penault-Llorca, Mei-Yin Polley, Roberto Salgado, Ian E. Smith, Tomoharu Sugie, John M. S. Bartlett, Lisa M. McShane, Mitch Dowsett, Daniel F. Hayes
Summary: Ki67 immunohistochemistry (IHC) is commonly used in breast cancer as a proliferation marker, but its analytical validity has been questioned. The International Ki67 in Breast Cancer Working Group (IKWG) recommends careful preanalytical handling, adoption of a standardized visual scoring method, and participation in quality assurance and quality control programs. Clinical utility of Ki67 IHC in breast cancer care is currently limited to prognosis assessment in stage I or II breast cancer.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Oncology
Y. Wang, B. Acs, S. Robertson, B. Liu, L. Solorzano, C. Wahlby, J. Hartman, M. Rantalainen
Summary: The study developed a novel histological grade model (DeepGrade) based on digital whole-slide histopathology images and deep learning to improve risk stratification of NHG 2 breast cancer patients. DeepGrade provides independent prognostic information for stratification of NHG 2 cases and adds clinically relevant information over routine histological grading, serving as a cost-effective alternative to extract relevant information for clinical decisions.
ANNALS OF ONCOLOGY
(2022)
Article
Genetics & Heredity
Emese Irma Agoston, Balazs Acs, Zoltan Herold, Krisztina Fekete, Janina Kulka, Akos Nagy, Dorottya Muhl, Reka Mohacsi, Magdolna Dank, Tamas Garay, Laszlo Harsanyi, Balazs Gyorffy, Attila Marcell Szasz
Summary: This study evaluated the expression of immune cells and immune checkpoint markers in colorectal cancer patients and found that cancer-related immunity plays a crucial role in the disease outcome. Gene expression analysis also identified differential expression of immune-related genes.
Article
Oncology
Una Kjallquist, Balazs Acs, Sara Margolin, Emelie Karlsson, Luisa Edman Kessler, Scarlett Garcia Hernandez, Maria Ekholm, Christine Lundgren, Erik Olsson, Henrik Lindman, Theodoros Foukakis, Alexios Matikas, Johan Hartman
Summary: This study investigates the impact of gene-expression-based risk testing on patient management in hormone receptor positive early breast cancer. The study finds that routine pathology factors are poor predictors of the intrinsic subtype and recurrence risk score, while gene-expression-based risk combined with clinicopathological biomarkers can guide adjuvant chemotherapy decisions.
Article
Pathology
Balazs Acs, Samuel C. Y. Leung, Kelley M. Kidwell, Indu Arun, Renaldas Augulis, Sunil S. Badve, Yalai Bai, Anita L. Bane, John M. S. Bartlett, Jane Bayani, Gilbert Bigras, Annika Blank, Henk Buikema, Martin C. Chang, Robin L. Dietz, Andrew Dodson, Susan Fineberg, Cornelia M. Focke, Dongxia Gao, Allen M. Gown, Carolina Gutierrez, Johan Hartman, Zuzana Kos, Anne-Vibeke Laenkholm, Arvydas Laurinavicius, Richard M. Levenson, Rustin Mahboubi-Ardakani, Mauro G. Mastropasqua, Sharon Nofech-Mozes, C. Kent Osborne, Frederique M. Penault-Llorca, Tammy Piper, Mary Anne Quintayo, Tilman T. Rau, Stefan Reinhard, Stephanie Robertson, Roberto Salgado, Tomoharu Sugie, Bert van der Vegt, Giuseppe Viale, Lila A. Zabaglo, Daniel F. Hayes, Mitch Dowsett, Torsten O. Nielsen, David L. Rimm
Summary: This study demonstrates certain comparability differences between core biopsy samples and corresponding resection specimens in Ki67 measurement, likely due to pre-analytical factors. Therefore, Ki67 immunohistochemistry should be tested on core biopsy samples as a priority to better reflect the biological status of the tumor.
Editorial Material
Oncology
Inne Nauwelaers, Nele Laudus, Dieter Peeters, Balazs Acs, Carsten Denkert, Stefan Michiels, Hugo Horlings, Kalliopi P. Siziopikou, Scott Ely, Dimitrios Zardavas, Roberts Mustimbo, John Bartlett, Giuseppe Floris, Johan Hartman, Carolien H. M. van Deurzen, Dorien Ceusters, Els Dequeker, Roberto Salgado
Summary: The article introduces a new training and proficiency program to improve pathologists' ability to score tumor infiltrating lymphocytes, and hence enhance the assessment of treatment response and prognosis.
Article
Oncology
Alexios Matikas, Hemming Johansson, Per Gryback, Judith Bjohle, Balazs Acs, Ceren Boyaci, Tobias Lekberg, Hanna Fredholm, Ellinor Elinder, Sara Margolin, Erika Isaksson-Friman, Ana Bosch, Henrik Lindman, Jamila Adra, Anne Andersson, Susanne Agartz, Mats Hellstrom, Ioannis Zerdes, Johan Hartman, Jonas Bergh, Thomas Hatschek, Theodoros Foukakis
Summary: PREDIX HER2 is a randomized Phase II trial that compared neoadjuvant docetaxel, trastuzumab, and pertuzumab (THP) with trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Rates of pathologic complete response (pCR) did not differ between the two groups. Here, we present the survival outcomes from PREDIX HER2 and investigate metabolic response and tumor-infiltrating lymphocytes (TIL) as prognostic factors.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Bianka Gurbi, Diana Brauswetter, Kinga Penzes, Attila Varga, Tibor Krenacs, Kornel Danos, Ede Birtalan, Laszlo Tamas, Miklos Csala
Summary: The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is due to the lack of prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is activated by overexpressed epidermal growth factor receptor (EGFR) and promotes the progression of HNSCCs. Our study investigated the effects of EGFR and MEK inhibitors on HNSCC-cell lines and found variations in sensitivity among different cell lines. The feedback activation of Akt through EGFR played a role in FaDu cells, while the insensitivity of Detroit 562 cells might be due to a PIK3CA mutation. The versatility of EGFR-initiated signaling pathways in HNSCC cell lines justifies the combined application of EGFR and MEK inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Attila Varga, Minh Tu Nguyen, Kinga Penzes, Bence Batai, Pal Gyulavari, Bianka Gurbi, Jozsef Muranyi, Peter Csermely, Miklos Csala, Tibor Vantus, Csaba Soti
Summary: Prostate cancer metastasis is a major cause of male mortality. Hsp90 promotes cancer cell migration by ensuring the conformational stability and function of PKD3, revealing a potential mechanism of Hsp90 in prostate cancer metastasis.
Article
Otorhinolaryngology
Judit Kalman, Tamas Horvath, Kornel Danos, Laszlo Tamas, Gabor Polony
Summary: The efficacy of ossicular chain reconstruction (OCR) in primary and revision surgeries was evaluated, and the impact of the number of previous surgeries on hearing outcomes was investigated. The study found that titanium prostheses are effective in both primary and revision surgeries, and the success of the surgery is influenced by the fact of revision rather than the number of previous surgeries.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Pato, Kata Bolcskei, Agnes Donko, Diana Kaszas, Melinda Boros, Lilla Bodrogi, Gyorgy Varady, Veronika F. S. Pape, Benoit T. Roux, Balaz Enyedi, Zsuzsanna Helyes, Fiona M. Watt, Gabor Sirokmany, Miklos Geszt
Summary: Keratinocytes of the mammalian skin produce hydrogen peroxide upon the activation of the NADPH oxidase dual oxidase 1 (DUOX1), which can be activated by increasing cytosolic calcium levels. DUOX1 knockout animals show increased sensitivity towards certain noxious stimuli, and this sensitivity is not due to structural changes in the skin. Hydrogen peroxide released by activated DUOX1 alters the activity of neuronal TRPA1 and redox-sensitive potassium channels in dorsal root ganglia primary sensory neurons, acting as a paracrine mediator of nociceptive signal transmission. These findings suggest a novel redox mechanism in modulating noxious sensory signals.
Article
Medicine, General & Internal
Thazin Nwe Aung, Saba Sha, James S. Wilmott, Saeed Nourmohammadi, Ioannis Vathiotis, Niki Gavrielatou, Aileen Fernandez, Vesal Yaghoobi, Tobias Sinnberg, Teresa Amaral, Kristian Ikenberg, Kiarash Khosrotehrani, Iman Osman, Balazs Acs, Yalai Bai, Sandra Martinez-Morilla, Myrto Mouta, John F. Thompson, Richard A. Scolyer, David L. Rimm
Summary: We evaluated the prognostic value of automated electronic TIL quantification in melanoma patients and found that electronic total TILs outperformed eTILs. We also identified the molecular subtype of TILs and their associations with survival outcomes.