Article
Oncology
Max J. Karlsson, Fernanda Costa Svedman, Abdellah Tebani, David Kotol, Veronica Hoiom, Linn Fagerberg, Fredrik Edfors, Mathias Uhlen, Suzanne Egyhazi Brage, Gianluca Maddalo
Summary: A study on malignant cutaneous melanoma identified potential biomarkers that could predict patient response to therapy, paving the way for personalized treatment strategies in the future.
Review
Oncology
Andrea Boutros, Enrica Teresa Tanda, Elena Croce, Fabio Catalano, Marcello Ceppi, Marco Bruzzone, Federica Cecchi, Luca Arecco, Matteo Fraguglia, Paolo Pronzato, Carlo Genova, Lucia Del Mastro, Matteo Lambertini, Francesco Spagnolo
Summary: The anti-LAG3 plus anti-PD-1 combination therapy has been approved as a treatment option for advanced melanoma. This study conducted a systematic review and network meta-analysis comparing different first-line treatment options in terms of progression-free survival, overall response rate, and treatment-related adverse events. The results showed that relatlimab/nivolumab had similar efficacy to ipilimumab/nivolumab but with a better safety profile.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Manali S. Phadke, Zhihua Chen, Jiannong Li, Eslam Mohamed, Michael A. Davies, Inna Smalley, Derek R. Duckett, Vinayak Palve, Brian J. Czerniecki, Peter A. Forsyth, David Noyes, Dennis O. Adeegbe, Zeynep Eroglu, Kimberly T. Nguyen, Kenneth Y. Tsai, Uwe Rix, Christin E. Burd, Yian A. Chen, Paulo C. Rodriguez, Keiran S. M. Smalley
Summary: In mouse models of BRAF- and NRAS-mutant melanoma, upfront immunotherapy enhances responses to targeted therapy. The sequence of IT -> TT modulates the immune environment, increasing infiltration of T cells and decreasing tumor-associated macrophages, leading to improved therapeutic outcomes. Durable responses to the IT -> TT sequence depend on T-cell activity and enrichment of a population of melanoma cells with increased expression of MHC class I and melanoma antigens.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Prachi Bhave, Lalit Pallan, Georgina V. Long, Alexander M. Menzies, Victoria Atkinson, Justine V. Cohen, Ryan J. Sullivan, Vanna Chiarion-Sileni, Marta Nyakas, Katharina Kahler, Axel Hauschild, Ruth Plummer, Claudia Trojaniello, Paolo A. Ascierto, Lisa Zimmer, Dirk Schadendorf, Clara Allayous, Celeste Lebbe, Andrea Maurichi, Mario Santinami, Severine Roy, Caroline Robert, Thierry Lesimple, Sapna Patel, Judith M. Versluis, Christian U. Blank, Adnan Khattak, Andre van der Westhuizen, Matteo S. Carlino, Mark Shackleton, Andrew Haydon
Summary: The study found that patients who relapse after adjuvant TT respond well to subsequent anti-PD-1 therapy, with outcomes similar to those seen when first-line anti-PD-1 therapy is used in stage IV melanoma.
BRITISH JOURNAL OF CANCER
(2021)
Article
Medicine, General & Internal
Pawel Rogala, Anna M. Czarnecka, Bozena Cybulska-Stopa, Krzysztof Ostaszewski, Karolina Piejko, Marcin Zietek, Robert Dziura, Ewa Rutkowska, Lukasz Galus, Natasza Kempa-Kaminska, Jacek Calik, Agata Salek-Zan, Tomasz Zemelka, Wieslaw Bal, Agnieszka Kamycka, Tomasz Switaj, Grazyna Kaminska-Winciorek, Rafal Suwinski, Jacek Mackiewicz, Piotr Rutkowski
Summary: Limited data is available on the sequencing of targeted therapy and immunotherapy in patients with BRAF-mutant melanoma. This study demonstrates the effectiveness of BRAFi/MEKi therapy as a second-line treatment for advanced melanoma patients, with similar efficacy observed for all combinations of BRAFi/MEKi.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Wolfram Samlowski, Camille Adajar
Summary: In patients with progressing melanoma after initial checkpoint inhibitor therapy, the addition of BRAF +/- MEK inhibitors to continued PD-1 antibody treatment as second line therapy showed substantial activity and manageable toxicity. This approach can induce durable complete responses in patients who have failed initial immunotherapy, suggesting further evaluation in suitable patients.
Article
Oncology
Adi Diab, Scott S. Tykodi, Gregory A. Daniels, Michele Maio, Brendan D. Curti, Karl D. Lewis, Sekwon Jang, Ewa Kalinka, Igor Puzanov, Alexander Spira, Daniel C. Cho, Shanhong Guan, Erika Puente, Tuan Nguyen, Ute Hoch, Sue L. Currie, Wei Lin, Mary A. Tagliaferri, Jonathan Zalevsky, Mario Sznol, Michael E. Hurwitz
Summary: This study found that the combination of BEMPEG and NIVO showed promising antitumor activity in first-line metastatic melanoma, including extended median progression-free survival. Early on-treatment blood biomarkers were associated with treatment response.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Oncology
Claudia Trojaniello, Francesca Sparano, Eleonora Cioli, Paolo Antonio Ascierto
Summary: This review discusses the efficacy and safety of sequential immunotherapy with targeted therapy in patients with BRAF-mutated melanoma. The findings suggest that targeted therapy provides rapid disease control, but the development of secondary resistance limits the duration of responses; in contrast, immunotherapy may induce slow but more durable responses. Therefore, a combination strategy for the use of these therapies seems promising.
CURRENT ONCOLOGY REPORTS
(2023)
Article
Cell Biology
Mingyue Liu, Xu Wang, Xuexiang Du, Wei Wu, Yan Zhang, Peng Zhang, Chunxia Ai, Martin Devenport, Juanjuan Su, Musleh M. Muthana, Lishan Su, Yang Liu, Pan Zheng
Summary: Immune checkpoint inhibitors (ICIs) like nivolumab and ipilimumab show both antitumor responses and severe immune-related adverse events (irAEs), but treating irAEs without affecting the immunotherapeutic effect of ICIs remains a challenge. The use of abatacept to treat irAEs risks reducing the efficacy of anti-CTLA-4 immunotherapy. However, mutants of CTLA-4-Ig that bind to B7-1 and B7-2 can effectively treat irAEs without affecting cancer immunotherapy, making belatacept a potential drug to abrogate irAEs while preserving the therapeutic efficacy of CTLA-4-targeting ICIs.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Dermatology
Franziska Noelle Harbers, Beatrice Thier, Simone Stupia, Si Zhu, Marion Schwamborn, Vicky Peller, Heike Chauvistre, Pietro Crivello, Katharina Fleischhauer, Alexander Roesch, Antje Sucker, Dirk Schadendorf, Yong Chen, Annette Paschen, Fang Zhao
Summary: Research found that the state transition of melanoma cells can profoundly affect the function of CD8+ tumor infiltrating lymphocytes, thereby impacting T cell responses to tumors. Melanoma cells undergoing hyperdifferentiation trajectory continuously increased sensitivity to tumor-reactive CD8+ T cells, while those in the dedifferentiation trajectory developed T cell resistance partly due to loss of differentiation antigens.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Oncology
Kristina V. Orlova, Evgeniy V. Ledin, Natalia V. Zhukova, Rashida V. Orlova, Elena V. Karabina, Mikhail V. Volkonskiy, Daniil L. Stroyakovskiy, Aleksandr N. Yurchenkov, Svetlana A. Protsenko, Alexey V. Novik, Ludmila V. Vorotilina, Fedor V. Moiseenko, Victor L. Chang, Aleksandr I. Kazmin, Svetlana A. Tkachenko, Sergey V. Gamaunov, David R. Naskhletashvili, Igor V. Samoylenko, Anastasia S. Vikhrova, Igor A. Utyashev, Galina Yu. Kharkevich, Natalia N. Petenko, Irina Zh. Shubina, Lev V. Demidov
Summary: Real-world data on treatment patterns and clinical outcomes for advanced BRAF V600 mutant melanoma patients are limited, but the study shows the effectiveness and good safety profile of combined TT with BRAF plus MEK inhibitors across all lines of therapy, including patients with brain metastases.
Article
Dermatology
Juliane Weilandt, Katharina Diehl, Marthe-Lisa Schaarschmidt, Felix Kiecker, Bianca Sasama, Melanie Pronk, Jan Ohletz, Andreas Koennecke, Verena Mueller, Jochen Utikal, Uwe Hillen, Wolfgang Harth, Wiebke K. Peitsch
Summary: The study showed that comorbidities significantly influence patients' treatment preferences for melanoma, with specific emphasis on factors such as treatment response time and route of administration, while showing less concern for overall response rate and treatment discontinuation.
JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT
(2021)
Article
Medicine, General & Internal
James R. Miller, Serigne N. Lo, Mehdi Nosrati, Jonathan R. Stretch, Andrew J. Spillane, Robyn P. M. Saw, Kerwin F. Shannon, Omgo E. Nieweg, Sydney Ch'ng, Kevin B. Kim, Stanley P. Leong, John F. Thompson, Richard A. Scolyer, Mohammed Kashani-Sabet
Summary: By refining eligibility guidelines, more appropriate patients can be identified to undergo useful medical procedures, improving cost-effectiveness in selecting patients with melanoma for sentinel lymph node biopsy (SLNB).
Article
Biochemistry & Molecular Biology
Anne Uebel, Stefanie Kewitz-Hempel, Edith Willscher, Kathleen Gebhardt, Cord Sunderkoetter, Dennis Gerloff
Summary: Activating BRAF mutations are present in 50-60% of malignant melanomas. Inhibiting EZH2 or its downstream target PLK1, in combination with BRAF inhibitors, may provide potential novel therapeutic options for melanomas with BRAF mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Brianna M. Lax, Joseph R. Palmeri, Emi A. Lutz, Allison Sheen, Jordan A. Stinson, Lauren Duhamel, Luciano Santollani, Alan Kennedy, Adrienne M. Rothschilds, Stefani Spranger, David M. Sansom, K. Dane Wittrup
Summary: Anti-CTLA-4 antibodies have limited long-term benefit in tumor regression. We engineered a nonantagonistic CTLA-4 binding domain and found that both CTLA-4 antagonism and intratumoral Treg depletion are needed for maximum efficacy in anti-CTLA-4 therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
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
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
Ali Can Sahillioglu, Ton N. Schumacher
Summary: The study developed a reversible PD-1-based T cell activation switch to control the activity of immunotherapy products, and explored the possibility space for improved second-generation switch systems. Through analyzing immune cell receptor docking and inhibitory signaling domains, it was found that inhibitory domains derived from myeloid cell receptors can most effectively suppress antigen receptor signaling in primary human T cells, and physical proximity of the inhibitory domain to the antigen receptor is crucial for efficiently inhibiting T cell activation.
HUMAN GENE THERAPY
(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)
Article
Multidisciplinary Sciences
Anastasia Gangaev, Elisa A. Rozeman, Maartje W. Rohaan, Olga I. Isaeva, Daisy Philips, Sanne Patiwael, Joost H. van den Berg, Antoni Ribas, Dirk Schadendorf, Bastian Schilling, Ton N. Schumacher, Christian U. Blank, John B. A. G. Haanen, Pia Kvistborg
Summary: PD-1 blockade may primarily affect T cell composition in peripheral blood, while CTLA-4 blockade may result in the expansion of melanoma-reactive CD8 T cell response in peripheral blood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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.
Editorial Material
Multidisciplinary Sciences
Anne M. van der Leun, Ton N. Schumacher
Article
Multidisciplinary Sciences
Joris L. Vos, Joris B. W. Elbers, Oscar Krijgsman, Joleen J. H. Traets, Xiaohang Qiao, Anne M. van der Leun, Yoni Lubeck, Iris M. Seignette, Laura A. Smit, Stefan M. Willems, Michiel W. M. van den Brekel, Richard Dirven, M. Baris Karakullukcu, Luc Karssemakers, W. Martin C. Klop, Peter J. F. M. Lohuis, Willem H. Schreuder, Ludi E. Smeele, Lilly-Ann van der Velden, I. Bing Tan, Suzanne Onderwater, Bas Jasperse, Wouter V. Vogel, Abrahim Al-Mamgani, Astrid Keijser, Vincent van der Noort, Annegien Broeks, Erik Hooijberg, Daniel S. Peeper, Ton N. Schumacher, Christian U. Blank, Jan Paul de Boer, John B. A. G. Haanen, Charlotte L. Zuur
Summary: The study demonstrated that neoadjuvant COMBO ICB is feasible and effective in treating HNSCC, with a significant proportion of patients showing a major pathological response of 90-100%. Additionally, FDG-PET imaging can help identify MPR patients prior to surgery in certain cases of HNSCC.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Elisa Matas-Rico, Elselien Frijlink, Irene van der Haar Avila, Apostolos Menegakis, Maaike van Zon, Andrew J. Morris, Jan Koster, Fernando Salgado-Polo, Sander de Kivit, Telma Lanc, Antonio Mazzocca, Zoe Johnson, John Haanen, Ton N. Schumacher, Anastassis Perrakis, Inge Verbrugge, Joost H. van den Berg, Jannie Borst, Wouter H. Moolenaar
Summary: The study reveals that ATX secreted by melanoma cells repels tumor-infiltrating lymphocytes and circulating CD8(+) T cells, acting as a chaperone for LPA. Mechanistically, T cell repulsion is mainly involved G alpha(12/13)-coupled LPAR6, suppressing CD8(+) T cell infiltration and affecting tumor regression.
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)