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
Oncology
Martin Lauss, Marco Donia, Inge Marie Svane, Goran Jonsson
Summary: Tumor-associated B cells and tertiary lymphoid structures (TLS) play important roles in cancer immunology. B cells have various functions such as antigen presentation, antibody production, and regulation. TLSs in tumors show substantial heterogeneity and support immune response. Current research is exploring the role of TLSs in immunotherapy, and results indicate that TLSs are beneficial for patient prognosis.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Jean-Yves Blay, Sylvie Chevret, Axel Le Cesne, Mehdi Brahmi, Nicolas Penel, Sophie Cousin, Francois Bertucci, Emmanuelle Bompas, Thomas Ryckewaert, Pauline Soibinet, Pascaline Boudou-Rouquette, Esma Saada Bouzid, Patrick Soulie, Thibaud Valentin, Jean-Pierre Lotz, Diego Tosi, Zoe Neviere, Mathilde Cancel, Isabelle Ray-Coquard, Laetitia Gambotti, Frederic Legrand, Assia Lamrani-Ghaouti, Clotilde Simon, Caroline Even, Christophe Massard
Summary: This study evaluated the activity of pembrolizumab in rare and ultra-rare sarcomas. The results showed that pembrolizumab displayed manageable activity and toxicity in selected histotypes of rare sarcomas, supporting the PD-1/PD-L1 pathway as a potential therapeutic target.
Article
Oncology
Catherine Sarre-Lazcano, Sinziana Dumitra, Marco Fiore
Summary: Pelvic soft tissue sarcomas (PSTS) are a rare and heterogeneous group of tumors that differ from retroperitoneal sarcomas (RPS). Adequate imaging and preoperative biopsy are crucial for differential diagnosis and treatment planning. Surgical approach and multidisciplinary teamwork are essential due to anatomic constraints and potential complications. Early referral to specialized centers is recommended for optimal resection and improved survival. International consensus on PSTS treatment is needed, similar to recent efforts for RPS.
Article
Oncology
Antoine Italiano, Derek Dinart, Isabelle Soubeyran, Carine Bellera, Helene Esperou, Christelle Delmas, Noemie Mercier, Sabrina Albert, Ludivine Poignie, Anne Boland, Aurelien Bourdon, Damien Geneste, Quentin Cavaille, Yec'han Laizet, Emmanuel Khalifa, Celine Auzanneau, Barbara Squiban, Nathalene Truffaux, Robert Olaso, Zuzana Gerber, Cedrick Wallet, Antoine Benard, Jean-Yves Blay, Pierre Laurent-Puig, Jean-Francois Deleuze, Carlo Lucchesi, Simone Mathoulin-Pelissier
Summary: The MULTISARC trial is a prospective study designed to provide high-level evidence to support the implementation of NGS in routine clinical practice for advanced STS participants, on a large scale.
Article
Cell Biology
Anthony B. Rodriguez, J. David Peske, Amber N. Woods, Katie M. Leick, Ileana S. Mauldin, Max O. Meneveau, Samuel J. Young, Robin S. Lindsay, Marit M. Melssen, Salwador Cyranowski, Geoffrey Parriott, Mark R. Conaway, Yang-Xin Fu, Craig L. Slingluff, Victor H. Engelhard
Summary: The study reveals that the development of tumor-associated tertiary lymphoid structures (TA-TLS) is orchestrated by cancer-associated fibroblasts (CAF) with characteristics of lymphoid tissue organizer cells, mediated by CD8 T cells and CXCL13-mediated recruitment of B cells. The presence and size of TA-TLS are correlated with reduced tumor size and overall response to checkpoint immunotherapy, providing a potential platform for cancer immunotherapy strategy.
Review
Immunology
Alessandra Vaccaro, Tiarne van de Walle, Mohanraj Ramachandran, Magnus Essand, Anna Dimberg
Summary: Tertiary lymphoid structures (TLS) are lymph node-like aggregates that form in association with chronic inflammation or cancer. They have been shown to have a positive prognosis and increased sensitivity to cancer immunotherapy. However, a comprehensive understanding of their role in anti-tumor immunity and the mechanisms involved in their formation and function is still lacking. Further research in relevant cancer models is needed to evaluate the impact of TLS on cancer therapies and develop new treatment approaches that promote their formation in cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Urology & Nephrology
Yuki Sato, Karina Silina, Maries van den Broek, Kiyoshi Hirahara, Motoko Yanagita
Summary: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that drive antigen-specific immune responses at sites of chronic inflammation. Their presence correlates with disease course, with favorable outcomes in cancer and infection, but more severe disease in autoimmune and chronic inflammatory diseases. However, the mechanisms underlying these associations are still unclear.
NATURE REVIEWS NEPHROLOGY
(2023)
Review
Immunology
Catarina Gago da Graca, Lisa G. M. van Baarsen, Reina E. Mebius
Summary: This review focuses on the role of lymph node stromal cells and TLSs in coordinating adaptive immune responses and their potential impact on diseases, particularly autoimmunity and cancer. The discussion includes recent findings on the function and formation of these structures and their possible role in promoting tolerance.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Meiying Wang, Snehin Rajkumar, Yupeng Lai, Xingjiao Liu, Jing He, Tatsuya Ishikawa, Dhiraj Nallapothula, Ram Raj Singh
Summary: This article describes the potential role of tertiary lymphoid structures (TLS) in the pathogenesis of autoimmune diseases, focusing on lupus nephritis. The presence of TLS in the kidneys is associated with severe inflammation, higher disease activity, and poor response to treatment. TLS may contribute to the development of lupus nephritis by increasing local immune response and supporting the production of autoantibodies. However, the mechanisms underlying TLS formation and their exact role in lupus nephritis are not fully understood.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Immunology
Lisa Schmidleithner, Markus Feuerer
Summary: A recent study reveals that repression of Satb1 in CD4(+) T cells can drive intratumoral TLS formation, resulting in reduced tumor growth.
TRENDS IN IMMUNOLOGY
(2022)
Review
Oncology
Changkai Zhou, Xue Chen, Ying Huang, Qi Zhang, Shu Zhu, Wei Fu
Summary: This article discusses the progress made in the use of nanotechnology for the diagnosis and treatment of soft tissue sarcomas (STS) and highlights the future prospects of STS multimodality therapy.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Rami Mustapha, Kenrick Ng, James Monypenny, Tony Ng
Summary: Tertiary lymphoid structures (TLS) can develop in chronic inflammation and cancer, potentially playing a role in adaptive antitumor immunity but also promoting cancer metastasis. The formation of TLS is closely related to the cytokine and chemokine signature, which is crucial for understanding cancer metastasis and developing cancer immunotherapeutics.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Nanda Horeweg, Hagma H. Workel, Dominik Loiero, David N. Church, Lisa Vermij, Alicia Leon-Castillo, Ricki T. Krog, Stephanie M. de Boer, Remi A. Nout, Melanie E. Powell, Linda R. Mileshkin, Helen MacKay, Alexandra Leary, Naveena Singh, Ina M. Juergenliemk-Schulz, Vincent T. H. B. M. Smit, Carien L. Creutzberg, Viktor H. Koelzer, Hans W. Nijman, Tjalling Bosse, Marco de Bruyn
Summary: B-cells and tertiary lymphoid structures (TLS) play critical roles in endometrial cancer (EC). L1CAM is identified as a marker for mature TLS and the presence of TLS is associated with favorable prognosis in EC patients.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Raj G. Vaghjiani, Joseph J. Skitzki
Summary: Tertiary lymphoid structures (TLS) are anatomical structures similar to but distinct from secondary lymphoid structures, allowing for a more targeted and efficient immune response. TLS are increasingly recognized as markers of prognosis and direct mediators of immunotherapy efficacy in cancer patients. The mechanisms and relationships of TLS in different tumors are being elucidated, with potential for TLS induction as a therapeutic avenue. This review discusses TLS formation, its relationship to malignancies, and its role in immunotherapy.
Article
Oncology
Bruno Vincenzi, Andrea Napolitano, Marta Fiocco, Olivier Mir, Piotr Rutkowski, Jean-Yves Blay, Peter Reichardt, Heikki Joensuu, Elena Fumagalli, Spyridon Gennatas, Nadia Hindi, Margherita Nannini, Mariella Spalato Ceruso, Antoine Italiano, Giovanni Grignani, Antonella Brunello, Silvia Gasperoni, Tommaso De Pas, Giuseppe Badalamenti, Maria A. Pantaleo, Winan J. van Houdt, Nikki S. IJzerman, Neeltje Steeghs, Hans Gelderblom, Ingrid M. E. Desar, Johanna Falkenhorst, Marianna Silletta, Marta Sbaraglia, Giuseppe Tonini, Javier Martin-Broto, Peter Hohenberger, Axel Le Cesne, Robin L. Jones, Angelo P. Dei Tos, Alessandro Gronchi, Sebastian Bauer, Paolo G. Casali
Summary: This study evaluated the effect of high-dose imatinib on the survival of patients with KIT exon 9-mutated gastrointestinal stromal tumors. The results showed that increasing the dose from 400 mg/day to 800 mg/day did not lead to better survival outcomes.
CLINICAL CANCER RESEARCH
(2022)
Letter
Oncology
Amandine Crombe, Mariella Spalato-Ceruso, Audrey Michot, Yech'an Laizet, Carlo Lucchesi, Maud Toulmonde, Kevin Bourcier, Francois Le Loarer, Antoine Italiano
CANCER COMMUNICATIONS
(2022)
Article
Oncology
A. Bessede, A. Marabelle, J. P. Guegan, F. X. Danlos, S. Cousin, F. Peyraud, N. Chaput, M. Spalato, G. Roubaud, M. Cabart, M. Khettab, A. Chaibi, C. Rey, I Nafia, F. X. Mahon, J. C. Soria, A. Italiano
Summary: The study reveals that acetaminophen (APAP) may suppress antitumor immunity and impact the efficacy of immunotherapy in cancer patients.
ANNALS OF ONCOLOGY
(2022)
Review
Oncology
Wolf H. Fridman, Maxime Meylan, Florent Petitprez, Cheng-Ming Sun, Antoine Italiano, Catherine Sautes-Fridman
Summary: B cells play a critical role in the tumor microenvironment, particularly within tertiary lymphoid structures (TLS). The presence of mature TLS, high density of B cells and plasma cells, and antibodies targeting tumor-associated antigens are associated with favorable clinical outcomes and response to immunotherapy. However, polyclonal B cell activation can lead to pro-inflammatory responses. Novel therapeutic approaches are being explored to enhance the development of TLS and anti-tumor B cells for cancer therapy.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Article
Oncology
Justine Gantzer, Guillaume Davidson, Bujamin Vokshi, Noelle Weingertner, Antoine Bougouin, Marco Moreira, Veronique Lindner, Guillaume Lacroix, Celine Mascaux, Marie-Pierre Chenard, Francois Bertucci, Irwin Davidson, Jean-Emmanuel Kurtz, Catherine Sautes-Fridman, Wolf H. Fridman, Gabriel G. Malouf
Summary: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) mainly have an immune desert tumor microenvironment (TME) and limited efficacy to immune checkpoint inhibitors (ICI). The TME of SMARCA4-driven tumors varies according to the cell of origin.
Editorial Material
Immunology
Catherine Sautes-Fridman, Anna Dimberg, Vivek Verma
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Lucia Carril-Ajuria, Aude Desnoyer, Maxime Meylan, Cecile Dalban, Marie Naigeon, Lydie Cassard, Yann Vano, Nathalie Rioux-Leclercq, Salem Chouaib, Benoit Beuselinck, Sylvie Chabaud, Janice Barros-Monteiro, Antoine Bougouin, Guillaume Lacroix, Irelka Colina-Moreno, Florence Tantot, Lisa Boselli, Caroline De Oliveira, Wolf Herve Fridman, Bernard Escudier, Catherine Sautes-Fridman, Laurence Albiges, Nathalie Chaput-Gras
Summary: The study investigated the potential predictive value of specific immune-cell populations and soluble factors in patients with m-ccRCC treated with nivolumab. It found that baseline levels of NSwM B cells were associated with response, PFS, and OS, while BCA-1/CXCL13 and BAFF were inversely correlated and associated with worse OS. Data confirms the role of B cell subsets in response to immune checkpoint blockade therapy in m-ccRCC patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Letter
Oncology
Mariella Spalato Ceruso, Maud Toulmonde, Laura Blouin, Antoine Italiano
EUROPEAN JOURNAL OF CANCER
(2023)
Letter
Oncology
Mariella Spalato-Ceruso, Fanny Bouteiller, Jean-Philippe Guegan, Maud Toulmonde, Alban Bessede, Michele Kind, Sophie Cousin, Xavier Buy, Jean Palussiere, Francois Le Loarer, Berengere Dadone-Montaudie, Marina Pulido, Antoine Italiano
Summary: The study investigates a strategy of using the G100 agonist to activate the TLR4 signaling pathway to improve the response to immunotherapy. Although G100 showed activity in improving the tumor microenvironment and T-cell infiltration, its clinical effectiveness in combination with PD1 inhibitors was limited.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Xiaofan Lu, Yann Vano, Alexandra Helleux, Xiaoping Su, Veronique Lindner, Guillaume Davidson, Roger Mouawad, Jean-Philippe Spano, Morgan Roupre, Reza Elaidi, Eva Comperat, Virginie Verkarre, Chengming Sun, Christine Chevreau, Mostefa Bennamoun, Herve Lang, Thibault Tricard, Wenxuan Cheng, Li Xu, Irwin Davidson, Fangrong Yan, Wolf Herman Fridman, Catherine Sautes-Fridman, Stephane Oudard, Gabriel G. Malouf
Summary: This study identified a novel epigenetic phenotype associated with resistance to immune checkpoint inhibitors (ICIs) in clear-cell renal cell carcinomas (ccRCC). This phenotype, called TED, was found to be associated with sarcomatoid differentiation, poor clinical outcome and resistance to first-line ipilimumab-nivolumab combination therapy. TED exhibited specific epigenetic alterations, gene expression signatures and tumor microenvironment characteristics.
CLINICAL CANCER RESEARCH
(2023)
Letter
Oncology
M. Spalato-Ceruso, A. Laroche-Clary, R. Perret, Y. Valverde, V Chaire, Marie-Alix Derieppe, V. Velasco, A. Bourdon, A. Italiano
Summary: Soft-tissue sarcoma (STS) is a rare and heterogeneous group of tumors with limited treatment options and high fatality rates. However, targeting ATM signaling network genes has been found to overcome resistance to ATR inhibition, as demonstrated by our CRISPR/Cas9 knockout models. Furthermore, the combination of ATM inhibitor AZD0156 and ATR inhibitor AZD6738 has shown synergistic effects, significantly inhibiting STS growth in vitro and inducing higher levels of DNA damage.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)
Letter
Oncology
Julie Blanchi, Sofiane Taleb, Arnaud Bayle, Benjamin Verret, Maud Toulmonde, Mariella Spalato-Ceruso, Paul Dubos, Yech'an Laizet, Melissa Alame, Emmanuel Khalifa, Antoine Italiano
CANCER COMMUNICATIONS
(2023)
Letter
Oncology
Yann-Alexandre Vano, Reza Elaidi, Letuan Phan, Maxime Meylan, Wolf Herman Fridman, Catherine Sautes-Fridman, Stephane Oudard
Letter
Oncology
Yann-Alexandre Vano, Reza Elaidi, Letuan Phan, Wolf Herman Fridman, Catherine Sautes-Fridman, Stephane Oudard
