Article
Pathology
Mai He, Priya Skaria, Kasey Kreutz, Ling Chen, Ian S. Hagemann, Ebony B. Carter, Indira U. Mysorekar, D. Michael Nelson, John Pfeifer, Louis P. Dehner
Summary: The study found that the maternal SARS-CoV-2 status does not have a significant effect on placental pathology, both in terms of pathological features and symptoms.
FETAL AND PEDIATRIC PATHOLOGY
(2022)
Article
Oncology
Fernanda G. Herrera, Catherine Ronet, Maria Ochoa de Olza, David Barras, Isaac Crespo, Massimo Andreatta, Jesus Corria-Osorio, Aodrenn Spill, Fabrizio Benedetti, Raphael Genolet, Angela Orcurto, Martina Imbimbo, Eleonora Ghisoni, Blanca Navarro Rodrigo, Dominik R. Berthold, Apostolos Sarivalasis, Khalil Zaman, Rafael Duran, Clarisse Dromain, John Prior, Niklaus Schaefer, Jean Bourhis, Georgia Dimopoulou, Zoi Tsourti, Marius Messemaker, Thomas Smith, Sarah E. Warren, Periklis Foukas, Sylvie Rusakiewicz, Mikael J. Pittet, Stefan Zimmermann, Christine Sempoux, Urania Dafni, Alexandre Harari, Lana E. Kandalaft, Santiago J. Carmona, Denarda Dangaj Laniti, Melita Irving, George Coukos
Summary: Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Low-dose radiation reprograms the tumor microenvironment to promote T-cell infiltration and, when combined with immunotherapy, simultaneously mobilizes innate and adaptive immunity, predominantly CD4(+) effector T cells, for tumor control dependent on NKG2D. This combination induces important responses in patients with metastatic immune-cold tumors.
Article
Oncology
Chetan C. Oturkar, Nishant Gandhi, Pramod Rao, Kevin H. Eng, Austin Miller, Prashant K. Singh, Emese Zsiros, Kunle O. Odunsi, Gokul M. Das
Summary: High grade serous ovarian cancer (HGSOC) is a common and deadly subtype of ovarian cancer with a high prevalence of mutant p53. This study investigated the interaction between estrogen receptor-beta (ER beta) and mutant p53 in HGSOC. The researchers found that ER beta 2 and mutant p53 co-dependently regulated the transcription of the FOXM1 gene, leading to increased cell proliferation and resistance to treatment. High levels of ER beta 2 and FOXM1 were correlated with worse patient survival. This suggests that targeting the ER beta 2-mutant p53-FOXM1 axis could be a novel therapeutic strategy for HGSOC.
Article
Biochemistry & Molecular Biology
Ute F. Roehrig, Somi Reddy Majjigapu, Pierre Vogel, Aline Reynaud, Florence Pojer, Nahzli Dilek, Patrick Reichenbach, Kelly Ascencao, Melita Irving, George Coukos, Olivier Michielin, Vincent Zoete
Summary: This study presents an extension of a highly efficient IDO1 inhibitor series, with the best compound showing strong inhibitory effects at both enzymatic and cellular levels. The research provides enzymatic inhibition data for nearly 100 new compounds and X-ray diffraction data for one compound in complex with IDO1, shedding light on the mechanisms behind the drop in activity observed in diverse haem-binding inhibitor scaffolds when extended to pocket B. These findings offer valuable insights for the future design of IDO1 inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Editorial Material
Cell Biology
Melita Irving, Yaquelin Ortiz-Miranda, George Coukos
Summary: IL-2 is a potent growth factor for T cells. Recent research has revealed that immune checkpoint blockade treatment relies on the presence of IL-2, and engineered mesenchymal stem cells can effectively deliver IL-2 directly in advanced tumors, rescuing CD8(+) T cell responsiveness to anti-PD-L1 antibody treatment.
NATURE CELL BIOLOGY
(2022)
Article
Oncology
Bianca Gautron Moura, Camille L. Gerard, Nathalie Testart, Marian Caikovski, Alexandre Wicky, Veronica Aedo-Lopez, Gregoire Berthod, Krisztian Homicsko, John O. Prior, Clarisse Dromain, Lana E. Kandalaft, Michel A. Cuendet, Olivier Michielin
Summary: In stage IV melanoma, the combination of ipilimumab and nivolumab significantly improves outcomes but has a major financial impact on healthcare. This study analyzes the costs associated with ipilimumab-nivolumab combination, focusing on immune-related adverse events (irAE). Surprisingly, toxicity costs are insignificant compared to the total treatment costs, and patients with higher toxicity grades have lower costs and better outcomes. These findings provide important information for clinicians and healthcare organizations making treatment decisions in immunotherapy.
Editorial Material
Oncology
Marion Arnaud, George Coukos, Alexandre Harari
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Mithila Sawant, Audrey Wilson, Dhivya Sridaran, Kiran Mahajan, Christopher J. O'Conor, Ian S. Hagemann, Jingqin Luo, Cody Weimholt, Tiandao Li, Juan Carlos Roa, Akhilesh Pandey, Xinyan Wu, Nupam P. Mahajan
Summary: Hormone receptor-positive, HER2-negative advanced breast cancers, which are sensitive to CDK4/6 inhibitors, often develop resistance. However, a study found that the non-receptor tyrosine kinase ACK1 is activated in breast cancer subtypes independent of hormone receptor status. Inhibition of ACK1 resulted in the suppression of cell cycle genes, leading to G2/M arrest and regression of palbociclib-resistant breast tumor growth. ACK1 inhibition also impaired the metastasis of breast cancer cells to the lung.
Article
Multidisciplinary Sciences
Julien Schmidt, Johanna Chiffelle, Marta A. S. Perez, Morgane Magnin, Sara Bobisse, Marion Arnaud, Raphael Genolet, Julien Cesbron, David Barras, Blanca Navarro Rodrigo, Fabrizio Benedetti, Alexandra Michel, Lise Queiroz, Petra Baumgaertner, Philippe Guillaume, Michael Hebeisen, Olivier Michielin, Tu Nguyen-Ngoc, Florian Huber, Melita Irving, Stephanie Tissot-Renaud, Brian J. Stevenson, Sylvie Rusakiewicz, Denarda Dangaj Laniti, Michal Bassani-Sternberg, Nathalie Rufer, David Gfeller, Lana E. Kandalaft, Daniel E. Speiser, Vincent Zoete, George Coukos, Alexandre Harari
Summary: This study explores the functional and structural avidities of T cell clones specific for different antigens and finds that T cells from tumors have stronger functional and structural avidities compared to those from blood. Neoantigen-specific T cells have higher structural avidity and are preferentially detected in tumors. Based on these findings, the researchers develop an in silico model to predict TCR structural avidity and validate the enrichment of high avidity T cells in patients' tumors.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ritaparna Ahmed, Leyder Elena Lozano, Amandine Anastasio, Sebastien Lofek, Beatris Mastelic-Gavillet, Blanca Navarro Rodrigo, Sylvain Nguyen, Florence Dartiguenave, Sonia-Cristina Rodrigues-Dias, Valerie Cesson, Massimo Valerio, Beat Roth, Lana Elias Kandalaft, Irina Redchenko, Adrian Vivian Sinton Hill, Alexandre Harari, Pedro Romero, Laurent Derre, Selena Vigano
Summary: Lymphocytes expanded from BPH tissue samples can recognize tumor antigens and autologous tissue independently from the presence of tumor lesions. These findings support the connection between BPH and prostate cancer and may lead to personalized preventive vaccination strategies for patients with BPH.
Article
Engineering, Biomedical
Patrick Reichenbach, Greta Maria Paola Giordano Attianese, Khaoula Ouchen, Elisabetta Cribioli, Melanie Triboulet, Sarah Ash, Margaux Saillard, Romain Vuillefroy de Silly, George Coukos, Melita Irving
Summary: This study reports the design and production of a lentiviral vector that incorporates two functionally independent promoters, allowing for the expression of a tumour-directed receptor and inducible gene in T cells. The vector enables the delivery of various genes to human T cells, improving the safety and efficacy of T-cell therapies.
NATURE BIOMEDICAL ENGINEERING
(2023)
Editorial Material
Oncology
Whitney R. Grither, Ian S. Hagemann, Matthew A. Powell, Mary M. Mullen
Summary: This article discusses the recent findings by Riedinger and colleagues regarding discordant mismatch repair and microsatellite instability testing in endometrial cancer.
Article
Biology
Emilee N. Kotnik, Mary M. Mullen, Nicholas C. Spies, Tiandao Li, Matthew Inkman, Jin Zhang, Fernanda Martins-Rodrigues, Ian S. Hagemann, Carolyn K. McCourt, Premal H. Thaker, Andrea R. Hagemann, Matthew A. Powell, David G. Mutch, Dineo Khabele, Gregory D. Longmore, Elaine R. Mardis, Christopher A. Maher, Christopher A. Miller, Katherine C. Fuh
Summary: Analysis of genomic and transcriptomic alterations in primary and metastatic tumors of high-grade serous ovarian cancer patients reveals differences associated with survival outcomes, providing insights for personalized treatment options and drug development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Sara Bobisse, Valentina Bianchi, Janos L. Tanyi, Apostolos Sarivalasis, Edoardo Missiaglia, Remy Petremand, Fabrizio Benedetti, Drew A. Torigian, Raphael Genolet, David Barras, Alexandra Michel, Spyridon A. Mastroyannis, Emese Zsiros, Denarda Dangaj Laniti, Zoi Tsourti, Brian J. Stevenson, Christian Iseli, Bruce L. Levine, Daniel E. Speiser, David Gfeller, Michal Bassani-Sternberg, Daniel J. Powell Jr, Carl H. June, Urania Dafni, Lana E. Kandalaft, Alexandre Harari, George Coukos
Summary: The study demonstrates that vaccination with tumor-pulsed dendritic cells enhances neoantigen recognition in ovarian cancer patients. Additionally, adoptive transfer of vaccine-primed, ex vivo-expanded autologous T cells further amplifies immune responses and leads to epitope spreading with novel neopeptide reactivities in patients who experience clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.
Article
Pharmacology & Pharmacy
Efthymia-Iliana Matthaiou, Yi Guo, Jaleh Barar, Raphael Sandaltzopoulos, Lana E. Kandalaft, Chunsheng Li, George Coukos, Yadollah Omidi
Summary: The study introduced a novel nanoformulation for targeted cancer therapy, demonstrating high toxicity against tumor cells and significant therapeutic effects in vivo. The nanoparticles showed high accumulation and effects in TEM1-positive tumor targets, with positive immune responses observed in animal models.
