Article
Cell Biology
Lutz Menzel, Maria Zschummel, Tadhg Crowley, Vedran Franke, Michael Grau, Carolin Ulbricht, Anja Hauser, Volker Siffrin, Marc Bajenoff, Sophie E. Acton, Altuna Akalin, Georg Lenz, Gerald Willimsky, Uta E. Hoepken, Armin Rehm
Summary: The study demonstrates that lymphoma leads to severe regression of high endothelial venules (HEVs) in the lymph nodes, disrupting immune cell trafficking and interactions in the microenvironment. This cascade of events involves the disruption of the lymph-carrying conduit system, deregulation of CCL21 migration paths, and loss of lymphotoxin-beta-receptor (LTbR) signaling, ultimately affecting HEV differentiation and lymphocyte transmigration.
Article
Oncology
Samantha M. Fix, Marie-Andree Forget, Donastas Sakellariou-Thompson, Yunfei Wang, Tamara M. Griffiths, Minjung Lee, Cara L. Haymaker, Ana Lucia Dominguez, Rafet Basar, Christopher Reyes, Sanjay Kumar, Larissa A. Meyer, Patrick Hwu, Chantale Bernatchez, Amir A. Jazaeri
Summary: In this study, we optimized CRISPR/Cas9-mediated knockout of TGF-beta receptor 2 (TGFBR2) in patient-derived ovarian cancer TIL. TGFBR2 knockout TIL showed resistance to immunosuppression and improved cytotoxicity. This lays the groundwork for clinical translation of CRISPR-modified TIL for the treatment of ovarian cancer and other solid cancers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Chantal Saberian, Rodabe N. Amaria, Amer M. Najjar, Laszlo G. Radvanyi, Cara L. Haymaker, Marie-Andree Forget, Roland L. Bassett, Silvana C. Faria, Isabella C. Glitza, Enrique Alvarez, Sapna Parshottam, Victor Prieto, Gregory Lizee, Michael K. Wong, Jennifer L. McQuade, Adi Diab, Cassian Yee, Hussein A. Tawbi, Sapna Patel, Elizabeth J. Shpall, Michael A. Davies, Patrick Hwu, Chantale Bernatchez
Summary: The combination of adoptive transfer of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC) did not show significant difference in the persistence of MART-1-specific TIL compared to TIL therapy alone. Although more patients showed clinical response to TIL+DC therapy, the study was not powered to resolve differences between the two groups.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Claire Y. Li, Hyeung Ju Park, Jinyeon Shin, Jung Eun Baik, Babak J. Mehrara, Raghu P. Kataru
Summary: This study suggests that lymphatic endothelial cells (LECs) can act as immunosuppressive cells in the tumor microenvironment (TME) in an MHC-II dependent manner. LECs in the TME increase MHC-II expression and co-inhibitory signals, suppressing the immune response. This finding highlights the importance of understanding the role of LECs in tumor immunity and opens up new avenues for therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Yifang Shui, Xin Hu, Hiroshi Hirano, Kisato Kusano, Hirotake Tsukamoto, Mengquan Li, Kenichiro Hasumi, Wen-Zhi Guo, Xiao-Kang Li
Summary: Dendritic cells play a crucial role in the immune response against tumors, but can be influenced by an immunosuppressive environment. Aureobasidium pullulan-derived beta-glucan has shown potential in enhancing the anti-tumoral activity of dendritic cells and inhibiting tumor growth.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Oncology
Veronica Finisguerra, Tereza Dvorakova, Matteo Formenti, Pierre Van Meerbeeck, Lionel Mignion, Bernard Gallez, Benoit J. van den Eynde
Summary: Despite limitations in certain tumor types and patients, immunotherapies have achieved revolutionary success in cancer treatment. However, the efficacy of immunotherapies is dependent on the viability and functionality of tumor antigen-specific CD8 T cells within the immunosuppressive tumor microenvironment, where oxygen levels are often low. This study reveals that the antidiabetic drug metformin can improve CD8 T cell fitness in hypoxia, increasing their proliferation and cytokine production, and enhancing their infiltration and survival in hypoxic tumor areas. This presents a promising strategy to overcome resistance to immunotherapy in hypoxic and immunosuppressive tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Xinyue Li, Jing Yang
Summary: This study investigated the relationship between tumor deposits and clinicopathological characteristics, tumor-infiltrating lymphocytes, and prognosis in gastric cancer. The results showed a significant association between tumor deposits and various characteristics and prognosis of gastric cancer, with patients having more than 4 tumor deposits having a worse prognosis.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2022)
Review
Oncology
Yueshui Zhao, Jian Deng, Shuangfeng Rao, Sipeng Guo, Jing Shen, Fukuan Du, Xu Wu, Yu Chen, Mingxing Li, Meijuan Chen, Xiaobing Li, Wanping Li, Li Gu, Yuhong Sun, Zhuo Zhang, Qinglian Wen, Zhangang Xiao, Jing Li
Summary: Cell-based immunotherapy, especially tumor-infiltrating lymphocytes (TILs) therapy, has emerged as a powerful strategy in solid cancer treatment. This review summarizes the current strategies and challenges in TIL generation, and discusses the clinical trials where TIL therapy is used independently or in combination with other therapies for solid tumor treatment. The limitations, future potential, and directions of TIL therapy for solid tumors are also discussed.
Article
Oncology
Jose Manuel Casanova, Jani-Sofia Almeida, John David Reith, Luana Madalena Sousa, Ruben Fonseca, Paulo Freitas-Tavares, Manuel Santos-Rosa, Paulo Rodrigues-Santos
Summary: Osteosarcoma is a common high-grade primary bone tumor that mainly affects young adults. The presence of tumor-infiltrating CD4+ cells is protective for patients, while CD8+ cells have a significant impact on overall survival and progression-free survival. There is a strong association between tumor-infiltrating CD4+ cells and CD44s expression in tumor samples, highlighting the importance of considering TIL and tumor markers for improving OST treatment.
Article
Oncology
Anders Handrup Kverneland, Christopher Aled Chamberlain, Troels Holz Borch, Morten Nielsen, Sofie Kirial Mork, Julie Westerlin Kjeldsen, Cathrine Lund Lorentzen, Lise Pyndt Jorgensen, Lene Buhl Riis, Christina Westmose Yde, Ozcan Met, Marco Donia, Inge Marie Svane
Summary: This study demonstrated high success rates of TIL expansion and tumor regressions in multiple solid cancer types when combining TIL ACT with CPIs. In vitro tumor reactivity was positively associated with treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Fumihiko Kinoshita, Tetsuzo Tagawa, Takaki Akamine, Kazuki Takada, Yuichi Yamada, Yuka Oku, Keisuke Kosai, Yuki Ono, Kensuke Tanaka, Sho Wakasu, Taro Oba, Atsushi Osoegawa, Mototsugu Shimokawa, Yoshinao Oda, Tomoaki Hoshino, Masaki Mori
Summary: High expression of IL-38 in tumor cells is significantly associated with reduced CD8(+)TILs and tumor progression, suggesting IL-38 could be a therapeutic target for lung cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Oncology
Yu Gao, Qi Luo, Zhichen Sun, Hannan Gao, Yue Yu, Yining Sun, Xiaotu Ma, Chuanhui Han, Jiyun Shi, Fan Wang
Summary: A new SPECT/CT imaging probe Tc-99m-sum IL-2 was developed to target tumor-infiltrating T cells and predict immune response and guide immunotherapy. The probe successfully identified tumor-infiltrating T cells and showed treatment efficacy through imaging.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Surbhi Bansil, Anthony Silva, Alana Taniguchi, Christina Wiedmer, Mayumi Fernandez, Ian Pagano, Koah Vierkoetter, Jeffrey Killeen, Jami Fukui
Summary: Tumor-infiltrating lymphocytes (TILs) have emerged as predictors of breast cancer treatment response and patient outcomes. This study provides preliminary data on the breast cancer tumor microenvironment for Asian and Native Hawaiian/Pacific Islander racial/ethnic groups, which are underrepresented in the literature.
Article
Oncology
Wei Shi, Mackenzie Fijardo, Jeff P. Bruce, Jie Su, Wei Xu, Rachel Bell, Pierre-Antoine Bissey, Angela B. Y. Hui, John Waldron, Trevor J. Pugh, Kenneth W. Yip, Fei-Fei Liu
Summary: This study reveals the prognostic significance of CD8+ tumor-infiltrating lymphocytes (TILs) in naso-pharyngeal cancer (NPC) and suggests the potential of utilizing CD8+ lymphocytes for immunotherapy.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Mikako Nishida, Nahoko Yamashita, Taisaku Ogawa, Keita Koseki, Eiji Warabi, Tomoyuki Ohue, Masaaki Komatsu, Hirokazu Matsushita, Kazuhiro Kakimi, Eiryo Kawakami, Katsuyuki Shiroguchi, Heiichiro Udono
Summary: Metformin stimulates oxidative stress in CD8TILs, promoting antitumor immunity, and combined treatment with anti-PD-1 antibody effectively inhibits tumor growth by altering the tumor microenvironment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Otorhinolaryngology
Pierre Gazda, Clement Gauche, Leonor Chaltiel, Emilien Chabrillac, Benjamin Vairel, Guillaume De Bonnecaze, Agnes Dupret-Bories, Thomas Filleron, Sebastien Vergez
Summary: This study confirms that survival and functional outcomes after salvage TORS are worse than in first line surgery.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2022)
Article
Allergy
Eve Blanquart, Audrey Mandonnet, Marion Mars, Claire Cenac, Nina Anesi, Pascale Mercier, Christophe Audouard, Stephane Roga, Gilberto Serrano de Almeida, Charlotte L. Bevan, Jean-Philippe Girard, Lucette Pelletier, Sophie Laffont, Jean-Charles Guery
Summary: This study investigates the impact of androgens on the development and function of innate lymphoid cells in female lungs. The findings suggest that androgens negatively control innate lymphoid cell homeostasis and inflammation in a cell-intrinsic manner. The inhibitory receptor killer cell lectin-like receptor G1 is found to play a dispensable role in androgen-mediated inhibition of innate lymphoid cells.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Oncology
Assia Asrir, Claire Tardiveau, Juliette Coudert, Robin Laffont, Lucas Blanchard, Elisabeth Bellard, Krystle Veerman, Sarah Bettini, Fanny Lafouresse, Estefania Vina, Dorian Tarroux, Severine Roy, Isabelle Girault, Irma Molinaro, Frederic Martins, Jean-Yves Scoazec, Nathalie Ortega, Caroline Robert, Jean-Philippe Girard
Summary: Tumor-associated high endothelial venules (TA-HEVs) are crucial for recruiting lymphocytes into tumors, and their presence is associated with better response and survival in anti-PD-1/anti-CTLA-4 treatment. TA-HECs co-express specific proteins and selectins, which attract lymphocytes to infiltrate tumors. Understanding the mechanism of lymphocyte trafficking in cancer immunity and immunotherapy is important for improving treatment outcomes.
Article
Oncology
Tina Lamy, Bastien Cabarrou, David Planchard, Xavier Quantin, Sophie Schneider, Michael Bringuier, Benjamin Besse, Nicolas Girard, Christos Chouaid, Thomas Filleron, Gaetane Simon, Capucine Baldini
Summary: This study compared the proportion of biomarker testing performed in older patients (>= 70 years old) and younger patients with non-squamous aNSCLC, showing no significant difference in testing frequency between the two age groups. Among older patients tested, 22% presented an EGFR mutation. These findings suggest that age is not a barrier to biomarker testing in patients with aNSCLC.
Meeting Abstract
Oncology
Veronique Dieras, Elise Deluche, Amelie Lusque, Barbara Pistilli, Thomas Bachelot, Jean-Yves Pierga, Frederic Viret, Christelle Levy, Laura Salabert, Fanny Le Du, Florence Dalenc, Christelle Jouannaud, Laurence Venat-Bouvet, Jean-Philippe Jacquin, Xavier Durando, Thierry Petit, Celine Mahier -Ait Oukhatar, Thomas Filleron, Maria Fernanda Mosele, Magali Lacroix-Triki, Agnes Ducoulombier, Fabrice Andre
Letter
Oncology
Leopoldine Lapierre, Charlotte Syrykh, Laetitia Largeaud, Bastien Cabarrou, Thomas Filleron, Lucie Oberic, Salim Kanoun, Lucie Coster, Camille Laurent, Benoit Branco, Noemie Gadaud, Christian Recher, Delphine Brechemier, Laurent Balardy, Francois Vergez, Loic Ysebaert, Martin Gauthier
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Health Care Sciences & Services
Bastien Cabarrou, Eve Leconte, Patrick Sfumato, Jean-Marie Boher, Thomas Filleron
Summary: In a heterogeneous population, the novel two-stage stratified adaptive phase II design provides a useful alternative to classical designs, allowing for the identification of a subgroup of interest without significantly increasing sample size. The design maintains competitive statistical power, controls type I error rates, and has a high probability of detecting heterogeneity, making it relevant not only for older populations but also for other study populations and the development of targeted therapies based on biomarkers.
BMC MEDICAL RESEARCH METHODOLOGY
(2022)
Article
Oncology
William Jacot, Amelie Lusque, Cecile Vicier, Audrey Mailliez, Thibault de La Motte Rouge, Luc Cabel, Christelle Levy, Anne Patsouris, Isabelle Desmoulins, Lionel Uwer, Jean-Christophe Thery, Mathieu Robain, Olivier Caron, Olivier Tredan, Thomas Filleron, Jean-Sebastien Frenel, Suzette Delaloge
Summary: In this study, the authors investigated the efficacy of platinum-based chemotherapy (PtCT) in patients with metastatic breast cancer (MBC) with and without germline BRCA1 or BRCA2 mutations. The results showed that first-line PtCT was associated with better progression-free survival (PFS) and overall survival (OS) in patients with gBRCA1/2 mutations, but not in those without mutations. These findings highlight the importance of early gBRCA1/2 testing in MBC patients.
BRITISH JOURNAL OF CANCER
(2022)
Article
Pathology
Anne-Cecile Brunac, Joanna Fourquet, Gaelle Perot, Marion Jaffrelot, Julie Meilleroux, Marie Danjoux, Thomas Filleron, Vincent Nicolai, Rosine Guimbaud, Samira Icher, Nadim Fares, Janick Selves, Frederic Chibon
Summary: The outcome of stage II-III colorectal cancer (CRC) varies greatly, and current therapeutic choices are based on TNM staging and a few additional biomarkers. However, a 67-gene expression prognostic signature called CINSARC has been developed and shown to have independent prognostic value in stage II-III CRC. This signature outperforms TNM staging and CMS classification in predicting recurrence-free and overall survival.
Article
Multidisciplinary Sciences
Fabrice Andre, Thomas Filleron, Maud Kamal, Fernanda Mosele, Monica Arnedos, Florence Dalenc, Marie-Paule Sablin, Mario Campone, Herve Bonnefoi, Claudia Lefeuvre-Plesse, William Jacot, Florence Coussy, Jean-Marc Ferrero, George Emile, Marie-Ange Mouret-Reynier, Jean-Christophe Thery, Nicolas Isambert, Alice Mege, Philippe Barthelemy, Benoit You, Nawale Hajjaji, Ludovic Lacroix, Etienne Rouleau, Alicia Tran-Dien, Sandrine Boyault, Valery Attignon, Pierre Gestraud, Nicolas Servant, Christophe Le Tourneau, Linda Larbi Cherif, Isabelle Soubeyran, Filippo Montemurro, Alain Morel, Amelie Lusque, Marta Jimenez, Alexandra Jacquet, Anthony Goncalves, Thomas Bachelot, Ivan Bieche
Summary: Cancer progression is driven by genomic alterations. Genomic profiling can help select effective therapies. A study on HER2-non-overexpressing metastatic breast cancer patients showed that targeted therapies matched to genomic alterations can improve progression-free survival, especially for patients with BRCA1/2 mutations.
Meeting Abstract
Hematology
Noemie Gadaud, Carlos Gomez Roca, Loic Ysebaert, Aurore Perrot, Myriam Estrabaut, Muriel Poublanc, Iphigenie Korakis, Christian Recher, Jean Pierre Delord, Thomas Filleron, Pierre Bories
Letter
Urology & Nephrology
Binghao Zhao, Ruidong Zhang, Jiamin Wu
Article
Oncology
Anne Laprie, Georges Noel, Leonor Chaltiel, Gilles Truc, Marie-Pierre Sunyach, Marie Charissoux, Nicolas Magne, Pierre Auberdiac, Julian Biau, Soleakhena Ken, Fatima Tensaouti, Jonathan Khalifa, Ingrid Sidibe, Franck-Emmanuel Roux, Laure Vieillevigne, Isabelle Catalaa, Sergio Boetto, Emmanuelle Uro-Coste, Stephane Supiot, Valerie Bernier, Thomas Filleron, Muriel Mounier, Muriel Poublanc, Pascale Olivier, Jean-Pierre Delord, Elizabeth Cohen-Jonathan-Moyal
Summary: MRSI-guided dose escalation in newly diagnosed GBM patients did not improve overall survival (OS).
Article
Medicine, Research & Experimental
Gaelen K. Dwyer, Lisa R. Mathews, Jose A. Villegas, Anna Lucas, Anne Gonzalez de Peredo, Bruce R. Blazar, Jean-Philippe Girard, Amanda C. Poholek, Sanjiv A. Luther, Warren Shlomchik, Heth R. Turnquist
Summary: In allogeneic hematopoietic stem cell transplantation (alloHCT), recipient conditioning releases damage-associated molecular patterns (DAMPs) that generate proinflammatory antigen-presenting cells (APCs) secreting IL-12, which drives the response of donor Th1 cells, leading to graft-versus-host disease (GVHD). However, there are other mechanisms through which alloreactive T cell responses are initiated by directly acting on donor CD4(+) T cells. Among these mechanisms, fibroblastic reticular cell-derived DAMP IL-33 plays a critical role by enhancing T cell expansion and differentiation through the activation of T cell signaling pathways in response to alloantigen, resulting in GVHD.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemical Research Methods
Lucas Blanchard, Estefania Vina, Assia Asrir, Claire Tardiveau, Juliette Coudert, Robin Laffont, Dorian Tarroux, Sarah Bettini, Krystle Veerman, Fanny Lafouresse, Melanie Pichery, Emilie Mirey, Elisabeth Bellard, Nathalie Ortega, Jean-Philippe Girard
Summary: This article presents a protocol for flow cytometry analysis of endothelial cells (ECs) and CD8+ T cells in murine tumor models, including baseline and post-immunotherapy analysis. The protocol is valuable for studying rare subsets of cells that play critical roles in antitumor immunity.