Article
Oncology
Cara Haymaker, Daniel H. Johnson, Ravi Murthy, Salah-Eddine Bentebibel, Marc Uemura, Courtney W. Hudgens, Houssein Safa, Marihella James, Robert H. Andtbacka, Douglas B. Johnson, Montaser Shaheen, Michael A. Davies, Shah Rahimian, Srinivas K. Chunduru, Denai R. Milton, Michael T. Tetzlaff, Willem W. Overwijk, Patrick Hwu, Nashat Gabrail, Sudhir Agrawal, Gary Doolittle, Igor Puzanov, Joseph Markowitz, Chantale Bernatchez, Adi Diab
Summary: The combination of intratumoral tilsotolimod and systemic ipilimumab shows promising results in patients with advanced melanoma, with an overall response rate of 22.4% and additional stability in 49% of patients. The phase III clinical trial of this combination is ongoing, indicating potential for improved clinical outcomes in a subset of patients resistant to traditional therapies.
Article
Pharmacology & Pharmacy
Wenxin Zhang, Xiaohui Pan, Yanjun Xu, Hongjie Guo, Mingming Zheng, Xi Chen, Honghai Wu, Fengming Luan, Qiaojun He, Ling Ding, Bo Yang
Summary: Mevalonate metabolism plays an important role in regulating tumor growth and progression. This study found that high plasma mevalonate levels positively correlated with better response to anti-PD-(L)1 therapy in NSCLC patients. Mevalonate supplementation up-regulated the expression of PD-L1 and improved CD274 mRNA stability, which enhanced the anti-tumor effect of anti-PD-L1 and improved T cell function.
ACTA PHARMACEUTICA SINICA B
(2023)
Review
Oncology
Alberto Carretero-Gonzalez, Irene Otero, David Lora, Lucia Carril-Ajuria, Daniel Castellano, Guillermo de Velasco
Summary: The study examines the benefits and risks of adding ICIs to standard of care, finding that adding ICIs can prolong survival with no early detrimental effect. Results show that ICIs arm has better PFS, OS, and ORR compared to SOC, although also associated with a slight increase in high-grade adverse events.
Article
Oncology
J. Randall Patrinely, Rebecca Johnson, Aleigha R. Lawless, Prachi Bhave, Amelia Sawyers, Maya Dimitrova, Hui Ling Yeoh, Marisa Palmeri, Fei Ye, Run Fan, Elizabeth J. Davis, Suthee Rapisuwon, Georgina V. Long, Andrew Haydon, Iman Osman, Janice M. Mehnert, Matteo S. Carlino, Ryan J. Sullivan, Alexander M. Menzies, Douglas B. Johnson
Summary: This multicenter cohort study found that chronic immune-related adverse events (irAEs) associated with anti-PD-1 therapy were more common than previously recognized, with a considerable proportion of patients developing chronic irAEs such as endocrinopathies and arthritis. Visceral organ-related irAEs had lower rates of becoming chronic, highlighting the importance of considering the risks of chronic irAEs in treatment decision-making.
Article
Immunology
Peidong Chi, Hang Jiang, Dandan Li, Jingjing Li, Xizhi Wen, Qiyue Ding, Linbin Chen, Xiaoshi Zhang, Junqi Huang, Ya Ding
Summary: This study found that by detecting immune cell subsets in the blood of melanoma patients, the progression-free survival rate of anti-PD-1 inhibitor treatment can be predicted. The immune risk score based on the absolute values of immune cell subsets can accurately predict which patients may benefit from ICI therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Yiqi Xu, Zhenyue Gao, Ruxin Hu, Yuqing Wang, Yuhong Wang, Zheng Su, Xiaoyue Zhang, Jingxuan Yang, Mei Mei, Yu Ren, Min Li, Xuan Zhou
Summary: Elevated and N-glycosylated PD-L2 levels were found in cetuximab-resistant HNSCC patients. Glycosylated PD-L2 formed a complex with EGFR, activating the EGFR/STAT3 signaling and reducing cetuximab binding. Inhibiting PD-L2 glycosylation increased cytotoxic T lymphocyte activity and enhanced response to cetuximab, suggesting a potential therapeutic strategy for cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Roberta Kif, Junko Johansson, Roger Olofsson Bagge, Anna Martner
Summary: The study demonstrates that the combination of melphalan-based therapy with PD-1 blockade shows significant reduction in early-stage tumor growth compared to monotherapies. The induction of PD-1 expression on CD8(+) tumor-infiltrating lymphocytes by melphalan-based therapy suggests a potential synergistic effect when combined with anti-PD-1 therapy.
Article
Immunology
Zihan Zhao, Siyang Liu, Rui Sun, Wenjie Zhu, Yulin Zhang, Tianyao Liu, Tianhang Li, Ning Jiang, Hongqian Guo, Rong Yang
Summary: Bladder cancer is a highly malignant tumor with limited improvement in prognosis and survival rates. Immune checkpoint inhibitors have revolutionized the treatment of bladder cancer, but their clinical application is limited by low response rates. This study investigated the combination of oxaliplatin and anti-PD-1 inhibitor in bladder cancer mouse models and found that this combination therapy was more efficient than medication alone.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Rachel S. Goodman, Aleigha Lawless, Rachel Woodford, Faisal Fa'ak, Asha Tipirneni, J. Randall Patrinely, Hui Ling Yeoh, Suthee Rapisuwon, Andrew Haydon, Iman Osman, Janice M. Mehnert, Georgina V. Long, Ryan J. Sullivan, Matteo S. Carlino, Alexander M. Menzies, Douglas B. Johnson
Summary: This retrospective cohort study analyzed 318 melanoma patients treated with adjuvant anti-PD-1 therapy and found that chronic irAEs were common and often persist with long-term follow-up, emphasizing the need for long-term monitoring and management.
Article
Oncology
Melissa L. Bastacky, Hong Wang, Dylan Fortman, Zahra Rahman, Gerard P. Mascara, Timothy Brenner, Yana G. Najjar, Jason J. Luke, John M. Kirkwood, Hassane M. Zarour, Diwakar Davar
Summary: This study of 190 metastatic melanoma patients treated with single-agent anti-PD-1 ICI therapy found that 60% experienced at least one immune-related adverse event (irAEs), with irAE occurrence significantly associated with response to anti-PD-1 therapy. Patients with multiple irAEs exhibited distinct patterns, and obesity was distinctly associated with irAE development, while age and gender showed no significant association.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Yiru Long, Xiaolu Yu, Runqiu Chen, Yongliang Tong, Likun Gong
Summary: With programmed death 1/ligand 1 (PD-1/PD-L1) as the cornerstone, anti-PD antibodies have revolutionized immunotherapies for malignancies. However, many patients fail to respond to anti-PD treatment due to resistance or hyperprogression. The study highlights the importance of noncanonical PD-1/PD-L1 expression in various cancers and its impact on the efficacy of anti-PD antibodies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Marisa E. Aikins, You Qin, Hannah E. Dobson, Alireza Hassani Najafabadi, Kexing Lyu, Yao Xu, Ying Xin, Anna Schwendeman, Max S. Wicha, Alfred E. Chang, Qiao Li, James J. Moon
Summary: One major obstacle in cancer treatment is the presence of cancer stem cells (CSCs), which are resistant to traditional therapies and contribute to metastasis and relapse. In this study, a therapeutic vaccine targeting CSCs in melanoma was developed and shown to effectively reduce tumor growth and improve survival. The vaccine stimulated strong T cell responses against CSC-associated antigens and promoted infiltration of CD8+ T cells into tumors, while reducing the frequency of CSCs. This approach represents a safe and cost-effective strategy for targeting and eliminating CSCs in melanoma and other types of cancer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Oncology
Prachi Bhave, Tasnia Ahmed, Serigne N. Lo, Alexander Shoushtari, Anne Zaremba, Judith M. Versluis, Joanna Mangana, Michael Weichenthal, Lu Si, Thierry Lesimple, Caroline Robert, Claudia Trojanello, Alexandre Wicky, Richard Heywood, Lena Tran, Kathleen Batty, Florentia Dimitriou, Anna Stansfeld, Clara Allayous, Julia K. Schwarze, Meghan J. Mooradian, Oliver Klein, Inderjit Mehmi, Rachel Roberts-Thomson, Andrea Maurichi, Hui-Ling Yeoh, Adnan Khattak, Lisa Zimmer, Christian U. Blank, Egle Ramelyte, Katharina C. Kaehler, Severine Roy, Paolo A. Ascierto, Olivier Michielin, Paul C. Lorigan, Douglas B. Johnson, Ruth Plummer, Celeste Lebbe, Bart Neyns, Ryan Sullivan, Omid Hamid, Mario Santinami, Grant A. McArthur, Andrew M. Haydon, Georgina Long, Alexander M. Menzies, Matteo S. Carlino
Summary: Acral melanoma is a rare subtype with poor prognosis, and there is a lack of prospective clinical trial evidence on the efficacy of checkpoint inhibitors in this population. The study found that initial anti-PD-1/ipilimumab combination had a significantly higher ORR compared to anti-PD-1 alone, but this benefit did not translate to improved OS in this retrospective cohort. Primary site did not impact treatment outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Junjie Liu, Haisu Tao, Tong Yuan, Jiang Li, Jian Li, Huifang Liang, Zhiyong Huang, Erlei Zhang
Summary: Anti-PD-1/PD-L1 therapy is an effective strategy for cancer treatment, but drug resistance is a challenge. Combining this therapy with regorafenib can enhance its efficacy. Regorafenib modifies the tumor microenvironment through various mechanisms and has immunomodulatory effects on immune cells and tumor cells. Studies on the synergistic mechanism of combination therapy can improve cancer treatment and patient selection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Haixia Long, Qingzhu Jia, Liuyang Wang, Wenfeng Fang, Zhongyu Wang, Tao Jiang, Fei Zhou, Zheng Jin, Jiani Huang, Li Zhou, Chunyan Hu, Xinxin Wang, Jin Zhang, Yujie Ba, Yujie Gong, Xianghua Zeng, Dong Zeng, Xingxing Su, Peter B. Alexander, Li Wang, Limei Wang, Yisong Y. Wan, Xiao-Fan Wang, Li Zhang, Qi-Jing Li, Bo Zhu
Summary: This study reveals a mechanism by which tumors exploit anemia-triggered erythropoiesis for myeloid transdifferentiation and immunosuppression.
Article
Biotechnology & Applied Microbiology
Marie Rouanet, Naima Hanoun, Hubert Lulka, Cindy Ferreira, Pierre Garcin, Martin Sramek, Godefroy Jacquemin, Agnes Coste, Delphine Pagan, Carine Valle, Emeline Sarot, Vera Pancaldi, Frederic Lopez, Louis Buscail, Pierre Cordelier
Summary: Toll-like receptors (TLRs) play a dual role in pancreatic cancer, inhibiting tumor cell proliferation and inducing cell death, but also potentially promoting tumor growth. Further investigations reveal that TLR7 agonists modulate the characteristics of tumor-associated macrophages, and depletion of these macrophages hampers TLR7 agonist-induced tumor growth.
Article
Biology
Pierre Cordelier, Manon Costa, Jerome Fehrenbach
Summary: This work studies models of oncolytic virotherapy without space variable, focusing on the relationship between the replication of the virus and tumor growth. The optimal timing and amount for virus injection in different treatment strategies are investigated. The research provides insights into the behavior of the system and discusses the timing of injections qualitatively. Numerical simulations are used for illustration and counterintuitive optimal values are found. The understanding of the system is clear from the phase space analysis.
BULLETIN OF MATHEMATICAL BIOLOGY
(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.
Article
Biotechnology & Applied Microbiology
Lorraine Quillien, Louis Buscail, Pierre Cordelier
Summary: Solid cancers present challenges in research due to their complex structure, genetic variations, and tumor microenvironment. Gene-based therapies offer diversity and complexity in tackling cancer, addressing limitations of traditional chemotherapies.
HUMAN GENE THERAPY
(2023)
Article
Oncology
Arnaud Carrier, Cecile Desjobert, Valerie Lobjois, Lise Rigal, Florence Busato, Jorg Tost, Miquel Ensenyat-Mendez, Diego M. Marzese, Anne Pradines, Gilles Favre, Laurence Lamant, Luisa Lanfrancone, Chantal Etievant, Paola B. Arimondo, Joelle Riond
Summary: Protocadherin proteins play an important role in cell adhesion and signaling pathways. The study found that the PCDHB15 gene's specific exon is hypermethylated in melanoma, leading to its silencing. This silencing contributes to the aggressiveness of melanoma.
CLINICAL EPIGENETICS
(2022)
Review
Oncology
Guillaume Le Cosquer, Charlotte Maulat, Barbara Bournet, Pierre Cordelier, Etienne Buscail, Louis Buscail
Summary: Chronic alcoholic pancreatitis is a major risk factor for pancreatic cancer. The risk is higher for hereditary pancreatitis, with PRSS1 and SPINK1 mutations having a risk of 19% and 12% respectively. The diagnosis is difficult due to the similarity in clinical and radiological features of chronic pancreatitis and pancreatic cancer. Endoscopic ultrasound-guided fine-needle biopsy with molecular biology can assist in diagnosis. Short-term follow-up is necessary for chronic pancreatitis patients with clinical and radiological suspicion of cancer, and pancreatic surgery may be required if doubt persists.
Letter
Urology & Nephrology
Binghao Zhao, Ruidong Zhang, Jiamin Wu
Article
Cell Biology
Nicolas Curdy, Olivia Lanvin, Juan-Pablo Cerapio, Frederic Pont, Marie Tosolini, Emeline Sarot, Carine Valle, Nathalie Saint-Laurent, Emeline Lhuillier, Camille Laurent, Jean-Jacques Fournie, Don-Marc Franchini
Summary: Stress granules (SGs) and processing bodies (PBs) are cytoplasmic assemblies that regulate mRNAs under environmental stress. This study characterizes the SGs and PBs in human T lymphocytes before and after stimulation using proteomic, transcriptomic, and immunofluorescence approaches. The findings reveal unexpected molecular and functional complementarity between SGs and PBs, although they maintain distinct spatial organizations and capacities to interact with mRNAs. This comprehensive characterization provides a valuable resource for future investigations on SGs and PBs in T lymphocytes.
Article
Medicine, Research & Experimental
Odile Barbey, Hubert Lulka, Naima Hanoun, Hafid Belhadj-Tahar, Fabienne Vernejoul, Gilles Cambois, Michele Tiraby, Louis Buscail, Fabian Gross, Pierre Cordelier
Summary: This study describes the development and evaluation of a non-viral gene therapy product called CYL-02 for pancreatic cancer. The product effectively delivers therapeutic genes to tumor cells and enhances their sensitivity to gemcitabine chemotherapy. The study demonstrates the safety and therapeutic potential of CYL-02 in experimental models of pancreatic cancer.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Chemistry, Physical
Abdelmnim Radoua, Baptiste Pernon, Nicolas Pernet, Chloe Jean, Mohammed Elmallah, Abderrahmane Guerrache, Andrei Alexandru Constantinescu, Sofiane Hadj Hamou, Jerome Devy, Olivier Micheau
Summary: This study presents an alternative non-viral delivery approach for CRISPR/Cas9, which allows efficient and flexible selection of knockout (KO) polyclonal cells. It reduces the time required to obtain a polyclonal isogenic cell line by 4-6 folds and provides a simple, fast, and cost-effective tool for genome editing.
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).
Review
Immunology
Marie Sorbara, Pierre Cordelier, Nicolas Bery
Summary: Pancreatic cancer is difficult to detect at an early stage and has limited treatment options due to drug resistance. Monoclonal antibodies show limited efficacy as a monotherapy, but present opportunities for treatment, diagnostics, and imagery.