Review
Oncology
Benjamin Wadowski, Raphael Bueno, Assunta De Rienzo
Summary: Malignant pleural mesothelioma is a rare and aggressive malignancy with limited treatment options, although immune checkpoint inhibition has shown some efficacy in a small subset of patients. Advances in next-generation sequencing technology have provided a better understanding of the molecular characteristics of MPM and its impact on the immune microenvironment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Medicine, Research & Experimental
Hajar Alemohammad, Basira Najafzadeh, Zahra Asadzadeh, Amir Baghbanzadeh, Farid Ghorbaninezhad, Arezoo Najafzadeh, Hossein Safarpour, Renato Bernardini, Oronzo Brunetti, Margherita Sonnessa, Rossella Fasano, Nicola Silvestris, Behzad Baradaran
Summary: The growth and development of cancer are directly correlated to the suppression of the immune system, with immune checkpoints playing a key role in inhibiting anti-tumor immune responses. Up-regulation of inhibitory immune checkpoints on immune cells during tumor progression suppresses anti-tumor immune responses and promotes immune escape. Targeting inhibitory immune checkpoints through antibodies or miRNAs is a promising therapeutic strategy, and immune checkpoint inhibitors have shown favorable results in enhancing immune cell-induced antitumor responses.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Oncology
Carly C. Barron, Isabella Stefanova, Yevin Cha, Karam Elsolh, Arman Zereshkian, Nessma Gaafour, Elaine McWhirter
Summary: Immune-related adverse events (irAEs) are toxicities resulting from use of immune checkpoint inhibitors (ICIs). These side effects persist in some patients despite withholding therapy and using immunosuppressive and immune-modulating agents. Little is known about chronic irAEs and they are felt to be rare.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Le He, Min Jin, Dan Jian, Bo Yang, Nan Dai, Yan Feng, He Xiao, Dong Wang
Summary: This study aimed to identify reliable transcriptome signatures to predict the efficacy of immune checkpoint blockade (ICB) in patients with rectal cancer. The study found that there are four stable immune subtypes in rectal cancer, and C3 and some C2 subtypes may benefit from ICB treatment after neoadjuvant chemoradiotherapy (nCRT).
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Yumin Zheng, Huijing Dong, Yixuan Yu, Zixin Hu, Chongxiang Xue, Xu Zhang, Huijuan Cui
Summary: This study aimed to summarize the treatment-related adverse events (trAEs) caused by immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors in patients with advanced lung cancer. The results showed that the incidence of trAEs was generally acceptable, with a wide spectrum of adverse events. Grade =3 trAEs were more commonly associated with angiogenesis inhibitors, but treatment-associated mortality remained of concern.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Oncology
Biagio Barone, Armando Calogero, Luca Scafuri, Matteo Ferro, Giuseppe Lucarelli, Erika Di Zazzo, Enrico Sicignano, Alfonso Falcone, Lorenzo Romano, Luigi De Luca, Francesco Oliva, Benito Fabio Mirto, Federico Capone, Ciro Imbimbo, Felice Crocetto
Summary: Bladder cancer is the ninth most common cancer worldwide. Immune checkpoint inhibitors have been used in neoadjuvant and adjuvant settings to improve the survival of bladder cancer patients. However, some patients do not respond to these drugs, and identifying eligible patients for this therapy is an ongoing effort. This review aims to summarize the latest evidence on the use of immune checkpoint inhibitors in the treatment of muscle-invasive bladder cancer.
Review
Agriculture, Dairy & Animal Science
Nicholas C. Kertz, Priyanka Banerjee, Paul W. Dyce, Wellison J. S. Diniz
Summary: This review discusses the genetic basis of fertility-related traits in cattle through the use of genomics and transcriptomics technologies. The authors highlight the opportunities and limitations of using these technologies to discover genes and regulatory mechanisms, and discuss the importance of translating research findings into on-farm applications.
Review
Immunology
Yang Liu, Shuo Liu, Yujun Qin, Lei Zhao, Yiliang Li, Chenghui Zhou, Wei Chen
Summary: Studies have shown that prior exposure to ICIs treatment does not increase the risk of COVID-19 infection and mortality compared to other antitumor treatments. ICIs may reduce the susceptibility to COVID-19 infection in metastatic cancer patients.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Guo Hong, Haina Zhao, Yuxuan Yin, Hailin Shen, Zhaohao Zeng, Jianwei Yang, Lili Zhang
Summary: The use of immune checkpoint inhibitors has been effective in treating various cancers, but it can also lead to immune-related adverse events. This paper reports a case of severe inflammatory myopathy in an esophageal cancer patient treated with Sintilimab. The incidence, mechanisms, and management strategies of fatal immune-related adverse events are discussed.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Patrizia Leone, Antonio Giovanni Solimando, Rossella Fasano, Antonella Argentiero, Eleonora Malerba, Alessio Buonavoglia, Luigi Giovanni Lupo, Valli De Re, Nicola Silvestris, Vito Racanelli
Summary: Hepatocellular carcinoma is a common and deadly cancer around the world. Traditional treatments like surgery, radiotherapy, and targeted therapies have been used, but due to the immune suppressive nature of HCC, immunotherapy with immune checkpoint inhibitors has shown great promise in recent clinical studies.
Review
Medicine, General & Internal
Norah A. A. Alturki
Summary: Checkpoint proteins are crucial for tumor cells to evade immune response, but immune checkpoint inhibitors can restore the immune system's ability to attack cancer cells. These inhibitors, such as CTLA-4, PD-1, PD-L1, have shown efficacy in treating various cancers and can be used alone or in combination with other treatments. They have fewer side effects compared to traditional chemotherapy drugs, but may still cause fatigue, skin rashes, and fever. Additionally, serious side effects like cardiotoxicity and inflammation can occur in rare cases. This article provides an overview of these inhibitors, their role as biomarkers, adverse effects, and clinical studies in cancer treatment, as well as future perspectives.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Immunology
Xiao-Juan Chen, Ai-Qun Ren, Liang Zheng, En-Dian Zheng
Summary: KDM5C alterations are associated with predictive value for cancer patients receiving ICIs, with patients having KDM5C alterations showing better survival rates. KDM5C alterations also correlate with increased tumor immunogenicity and anti-tumor immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ying Wang, Mengxue Yang, Mingyang Tao, Peipei Liu, Cheng Kong, Hao Li, Yingmei Chen, Xudong Yin, Xuebing Yan
Summary: The use of corticosteroids for cancer-related indications in lung cancer patients receiving ICI treatment is associated with poorer prognosis, as demonstrated by meta-analysis and retrospective analysis. Subgroup analysis focusing on non-small cell lung cancer (NSCLC) showed similar results, highlighting the importance of careful selection of corticosteroid-treated patients for ICI therapy in personalized clinical management.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Review
Immunology
Chen Lin, Guixiang Xu, Shuyan Gao, Tao Feng, Shuang Li
Summary: This study investigated the clinical features of active tuberculosis infection caused by immune checkpoint inhibitors (ICIs) treatment in patients with advanced cancer. A total of 23 patients were included in the study, and it was found that stopping ICIs therapy and administering anti-tuberculosis treatment can improve symptoms in most patients with tuberculosis, but attention should be paid to the potentially fatal risk of tuberculosis infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Jingjing Shen, Zhongming Wang
Summary: Immune checkpoint inhibitors have become an important treatment for advanced gastric cancer, with combination therapy showing better clinical efficacy, and numerous trials exploring more effective combination therapy programs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemical Research Methods
Feline E. Dijkgraaf, Mireille Toebes, Mark Hoogenboezem, Marjolijn Mertz, David W. Vredevoogd, Tiago R. Matos, Marcel B. M. Teunissen, Rosalie M. Luiten, Ton N. Schumacher
Summary: This ex vivo imaging approach allows for the study of immune cell behavior in human skin and can be applied to research on immune cell function in murine skin. The ability to track the spatiotemporal behavior of immune cells in skin, including their response to immune stimuli, provides a platform for investigating physiological immune cell behavior as well as immune cell behavior in skin diseases.
Article
Biochemistry & Molecular Biology
E. A. Rozeman, E. P. Hoefsmit, I. L. M. Reijers, R. P. M. Saw, J. M. Versluis, O. Krijgsman, P. Dimitriadis, K. Sikorska, B. A. van de Wiel, H. Eriksson, M. Gonzalez, A. Torres Acosta, L. G. Grijpink-Ongering, K. Shannon, J. B. A. G. Haanen, J. Stretch, S. Ch'ng, O. E. Nieweg, H. A. Mallo, S. Adriaansz, R. M. Kerkhoven, S. Cornelissen, A. Broeks, W. M. C. Klop, C. L. Zuur, W. J. van Houdt, D. S. Peeper, A. J. Spillane, A. C. J. van Akkooi, R. A. Scolyer, T. N. M. Schumacher, A. M. Menzies, G. V. Long, C. U. Blank
Summary: The combination of neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma. High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-gamma score) were associated with pathologic response and a low risk of relapse. These findings support the potential predictive value of TMB and IFN-gamma score in the treatment of melanoma patients.
Article
Cell Biology
Feline E. Dijkgraaf, Lianne Kok, Ton N. M. Schumacher
Summary: This article reviews the early signals received by CD8(+) T cells before entering tissues, as well as tissue-derived factors that promote Trm maturation in situ. The data presented sketch a model in which a subset of responding T cells develop a heightened capacity to respond to local cues in the tissue microenvironment, imprinting their ability to provide local control against pathogens in tissue-resident memory CD8(+) T-cell pool.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2021)
Review
Immunology
Mirjam E. Hoekstra, Saskia V. Vijver, Ton N. Schumacher
Summary: In the tumor micro-environment, activated CD8(+) T cells secrete cytokines like IFN gamma, TNF alpha, and IL-2, but the understanding of how these cytokines are sensed by other cells is limited. This review focuses on the behavior of these T-cell-secreted cytokines in the TME, proposing a model that suggests variations in cytokine secretion, half-life, clearance, and binding sculpt the tissue response to T-cell activation in cancer.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Anastasia Gangaev, Steven L. C. Ketelaars, Olga I. Isaeva, Sanne Patiwael, Anna Dopler, Kelly Hoefakker, Sara De Biasi, Lara Gibellini, Cristina Mussini, Giovanni Guaraldi, Massimo Girardis, Cami M. P. Talavera Ormeno, Paul J. M. Hekking, Neubury M. Lardy, Mireille Toebes, Robert Balderas, Ton N. Schumacher, Huib Ovaa, Andrea Cossarizza, Pia Kvistborg
Summary: This study identified a range of SARS-CoV-2 CD8(+) T cell responses across COVID-19 patients, including an epitope from ORF1ab with immunodominant features. The specific CD8(+) T cell responses can still be detectable up to 5 months after recovery from critical and severe disease, converting from dysfunctional effector cells to functional memory cells during convalescence.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Ali Can Sahillioglu, Ton N. Schumacher
Summary: The development of genetic safety switches to control the activity of T cells in vivo has become an active research field. These switches can reversibly control cell products through the supply or removal of small molecules, protein-based regulators, or physical stimuli. Various mechanistic classes of genetic safety switches are discussed in this review.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anne M. van der Leun, Mirjam E. Hoekstra, Luuk Reinalda, Colinda L. G. J. Scheele, Mireille Toebes, Michel J. van de Graaff, Hanjie Li, Akhiad Bercovich, Yaniv Lubling, Eyal David, Daniela S. Thommen, Amos Tanay, Jacco van Rheenen, Ido Amit, Sander van Kasteren, Ton N. Schumacher
Summary: The study introduces a photocage-based technology that allows isolation and in-depth analysis of live cells from complex ex vivo systems, including primary human tissues. By using nanobodies and a highly sensitive 4-nitrophenyl(benzofuran) cage, high-resolution photo-uncaging of different cell types in areas of interest is achieved.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paula Voabil, Marjolein de Bruijn, Lisanne M. Roelofsen, Sanne H. Hendriks, Simone Brokamp, Marlous van den Braber, Annegien Broeks, Joyce Sanders, Petra Herzig, Alfred Zippelius, Christian U. Blank, Koen J. Hartemink, Kim Monkhorst, John B. A. G. Haanen, Ton N. Schumacher, Daniela S. Thommen
Summary: A study using patient-derived tumor fragments as an ex vivo platform showed that the reactivation of tumor-infiltrating immune cells after PD-1 blockade could predict clinical outcomes. Tumor-resident T cells were identified as crucial in the immunological response, and a subgroup of tumors was found to be unresponsive to PD-1 blockade. Additionally, the presence of tertiary lymphoid structures in baseline tumors correlated with the capacity for intratumoral immune cell reactivation.
Article
Oncology
Victoria S. Pelly, Agrin Moeini, Lisanne M. Roelofsen, Eduardo Bonavita, Charlotte R. Bell, Colin Hutton, Adrian Blanco-Gomez, Antonia Banyard, Christian P. Bromley, Eimear Flanagan, Shih-Chieh Chiang, Claus Jorgensen, Ton N. Schumacher, Daniela S. Thommen, Santiago Zelenay
Summary: By profiling mice and human tumors, this study identifies mechanisms by which anti-inflammatory drugs rapidly alter the tumor immune landscape to enhance tumor immunogenicity and responses to immune checkpoint inhibitors.
Article
Oncology
Ali Can Sahillioglu, Mireille Toebes, Georgi Apriamashvili, Raquel Gomez, Ton N. Schumacher
Summary: A small-molecule responsive genetic safety switch has been developed to restore or block the activity of T cells by controlling drug administration, providing a new approach for tumor therapy with reversibility and titratability. This switch can be combined with various T cell receptors, making it a universal and versatile platform for regulating the activity of cell products.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Noor Alida Maria Bakker, Jossie Rotman, Marc van Beurden, Henry J. M. A. Zijlmans, Maartje van Ruiten, Sanne Samuels, Bastiaan Nuijen, Jos Beijnen, Karin De Visser, John Haanen, Ton Schumacher, Tanja de Gruijl, Ekaterina S. Jordanova, Gemma G. Kenter, Joost H. van den Berg, Nienke E. van Trommel
Summary: The HPV-16 E6/E7 DNA tattoo vaccination is an effective and safe treatment strategy for patients with uVIN, with HPV-specific T-cell responses being associated with clinical benefit.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Meeting Abstract
Oncology
W. Scheper, C. Cattaneo, J. Urbanus, T. Battaglia, J. B. A. G. Haanen, E. E. Voest, T. N. Schumacher
ANNALS OF ONCOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Muhammad Ali, Eirini Giannakopoulou, Yingqian Li, Madeleine Lehander, Stina Virding Culleton, Weiwen Yang, Cathrine Knetter, Mete Can Odabasi, Ravi Chand Bollineni, Xinbo Yang, Zsofia Foldvari, Maxi-Lu Boschen, Eli Taraldsrud, Erlend Stronen, Mireille Toebes, Amy Hillen, Stefania Mazzi, Arnoud H. de Ru, George M. C. Janssen, Arne Kolstad, Geir Erland Tjonnfjord, Benedicte A. Lie, Marieke Griffioen, Soren Lehmann, Liv Toril Osnes, Jochen Buechner, K. Christopher Garcia, Ton N. Schumacher, Peter A. van Veelen, Matthias Leisegang, Sten Eirik W. Jacobsen, Petter Woll, Johanna Olweus
Summary: T cells modified with TCRs targeting TdT can specifically eliminate acute lymphoblastic leukemia cells while sparing normal lymphocytes. TdT is highly expressed in cancer cells but transiently expressed in normal cells, thus limiting the toxicity of T cell targeting TdT.
NATURE BIOTECHNOLOGY
(2022)
Review
Multidisciplinary Sciences
Ton N. Schumacher, Daniela S. Thommen
Summary: This article discusses the current knowledge on TLSs in cancer, focusing on the drivers of TLS formation, the function and contribution of TLSs to the antitumor immune response, and the potential of TLSs as therapeutic targets in human cancers.
Review
Immunology
Lianne Kok, David Masopust, Ton N. Schumacher
Summary: CD8(+) tissue resident memory T cells are crucial for immune defence against pathogens and malignancies. While it was previously believed that these cells formed locally within inflamed tissue, emerging evidence suggests the existence of circulating T-RM cell precursors. This review discusses the formation of T-RM cells and the signals within the lymphoid compartment that influence their lineage decisions.
NATURE REVIEWS IMMUNOLOGY
(2022)