Review
Oncology
Francesca Perutelli, Rebecca Jones, Valentina Griggio, Candida Vitale, Marta Coscia
Summary: Immune-based therapeutic strategies have revolutionized the treatment of hematological disorders by enhancing the immune response against tumor cells. However, individual use of immunotherapy has not shown optimal results in terms of disease control due to CLL-related immune dysfunctions. The understanding of the interactions between immune cells and tumor cells has led to the development of novel combination approaches that hold promise for future treatment of CLL.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Michaela Allison, Joel Mathews, Taylor Gilliland, Stephen O. Mathew
Summary: This review describes the functional impairment of NK cells in leukemia and current NK cell immunotherapies under investigation, including mAbs, adoptive transfer, and CAR-NKs. NK cells play a critical role in cancer cell elimination through recognition and cytolysis of abnormal cell populations.
Review
Oncology
Max Yano, John C. Byrd, Natarajan Muthusamy
Summary: This article reviews the potential and progress of NK cell therapy for CLL, highlighting the immunosuppressive effects of CLL on NK cells as a major limitation to the development of effective treatments. Despite the challenges, NK cell therapy still holds significant therapeutic potential for CLL.
Article
Multidisciplinary Sciences
Chengxin Luo, Guixian Wu, Xiangtao Huang, Yanni Ma, Yali Zhang, Qiuyue Song, Mingling Xie, Yanni Sun, Yarui Huang, Zhen Huang, Yu Hou, Shuangnian Xu, Jieping Chen, Xi Li
Summary: In comparing new anti-CD20 monoclonal antibodies with rituximab in the induction therapy of CD20(+) B-NHL, it was found that obinutuzumab significantly improved PFS but had higher incidence of adverse events, ofatumumab decreased ORR, and Y-90-ibritumomab tiuxetan increased ORR.
SCIENTIFIC REPORTS
(2021)
Review
Immunology
Siqin Duan, Shuwen Liu
Summary: This review highlights the immunotherapy strategies for HIV infection that utilize the beneficial properties of natural killer (NK) cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Paolo Sportoletti, Filomena De Falco, Beatrice Del Papa, Stefano Baldoni, Valerio Guarente, Andrea Marra, Erica Dorillo, Chiara Rompietti, Francesco Maria Adamo, Loredana Ruggeri, Mauro Di Ianni, Emanuela Rosati
Summary: Key features of CLL include immune system defects and leukemic cells’ ability to evade immune defenses, leading to increased susceptibility to infections and disease progression. The role of NK cells in CLL is less understood, but evidence suggests that NK cell dysfunctions in CLL mainly depend on escape mechanisms employed by leukemic cells. NK cells, with their preserved ADCC function and reversible dysfunctions, are an attractive source for novel immunotherapeutic strategies in CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Phatchanat Klaihmon, Xing Kang, Surapol Issaragrisil, Sudjit Luanpitpong
Summary: Natural killer (NK) cells can be rapidly activated to target tumor antigens without prior sensitization, making them a promising alternative to CAR-T cells for cellular immunotherapy. Human induced pluripotent stem cells (iPSCs) are a renewable source for clinical NK cells. In this study, a third-generation CAR targeting CD19 was successfully introduced into umbilical cord blood NK-derived iPSCs, resulting in the generation of CAR19-iNK-like cells with improved anti-tumor activity compared to wild-type (WT) iNK-like cells. This approach provides a feasible alternative source for off-the-shelf CAR-NK cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Francesco Maria Adamo, Estevao Carlos Silva Barcelos, Filomena De Falco, Erica Dorillo, Chiara Rompietti, Daniele Sorcini, Arianna Stella, Beatrice Del Papa, Stefano Baldoni, Angela Esposito, Clelia Geraci, Roberta Arcaleni, Chiara Pennetta, Francesco Ragonese, Lorenzo Moretti, Mariagrazia Mameli, Mauro Di Ianni, Emanuela Rosati, Bernard Fioretti, Paolo Sportoletti
Summary: In this study, the cytotoxicity of silver nanoparticles (AgNPs) against chronic lymphocytic leukemia (CLL) cells was highlighted, and the synergistic activity of AgNPs with drugs currently used in CLL, such as Venetoclax and Ibrutinib, was demonstrated. The conjugation of AgNPs with the anti-CD20 antibody Rituximab (AgNPs@Rituximab) increased the specificity and cytotoxicity of AgNPs toward CLL cells in vitro. AgNPs@Rituximab also extended the survival of CLL xenograft models compared to each unconjugated single agent.
Article
Immunology
Ludivine Grzelak, Ferdinand Roesch, Amaury Vaysse, Anne Biton, Rachel Legendre, Francoise Porrot, Pierre-Henri Commere, Cyril Planchais, Hugo Mouquet, Marco Vignuzzi, Timothee Bruel, Olivier Schwartz
Summary: This study identified Interferon Regulatory Factor 8 (IRF8) as a gene involved in regulating the efficacy of anti-CD20 antibodies. The results demonstrated that IRF8 is necessary for efficient CD20 transcription, and its presence is positively correlated with CD20 expression and the depleting capacity of anti-CD20 antibodies.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Oncology
Kate J. Dixon, Jianming Wu, Bruce Walcheck
Summary: Human natural killer (NK) cells target tumor antigens through interaction with IgG Fc receptors, leading to antibody-dependent cell-mediated cytotoxicity (ADCC) against cancer cells. Engineering monoclonal antibodies and Fc receptors can enhance NK cell-mediated ADCC for cancer treatment. Targeting tumor antigens by modifying the Fc portion of antibodies or the FcR on NK cells is a key focus of research in improving mAb therapy efficacy.
Review
Immunology
Hans Klingemann
Summary: Dogs still face challenges in cancer immunotherapies, including high costs, lack of targetable surface antigens, and cancer's immunosuppressive nature. Developing tailored treatments for canines is limited, but there is hope that addressing these issues will help dogs catch up with human treatments.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Nurul Izza Ismail
Summary: As the placenta is semi-allogenic, it is expected that maternal immune cells would attack the invading trophoblast, but studies have shown that they cooperate with the trophoblast to disrupt the arterial wall. uNK cells, unique immune cells, play a role in pregnancy. The interaction between HLA class 1b genes and maternal uNK cells in humans is described in this review.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Oluwatobi Odetola, Shuo Ma
Summary: This review emphasizes that the purpose of treatment for relapsed/refractory CLL is disease control and delay of progression rather than cure. The article reviews the concept of relapsed CLL, factors predisposing to relapse, and available therapeutic options. Recent findings show that targeted therapies such as continuous BTK inhibitors or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy have established superiority over chemoimmunotherapy in relapsed CLL and are now the preferred standard of care treatment.
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
(2023)
Article
Oncology
Shance Li, Chaoting Zhang, Luyan Shen, Xia Teng, Yefei Xiao, Bentong Yu, Zheming Lu
Summary: NK cells can be engineered for TCR therapy in tumor treatment. A chimeric TCR NK cell was designed and showed antigen-specific recognition and cytotoxicity. This approach has potential clinical applications.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Hyeree Choi, Michelle Ho, Opeyemi S. Adeniji, Leila Giron, Devivasha Bordoloi, Abhijeet J. Kulkarni, Alfredo Perales Puchalt, Mohamed Abdel-Mohsen, Kar Muthumani
Summary: A panel of human anti-Siglec-9 hybridoma clones with high specificity and functionality were developed through immunizing mice with Siglec-9-encoding DNA and protein. The lead antibodies were found to enhance anti-tumor immune activity in vitro and significantly reduce tumor volume in an ovarian cancer humanized mouse model. These novel antibodies interfere with Siglec-9-mediated immunosuppression to augment anti-tumor immunity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Immunology
Satoshi Nakamizo, Charles-Antoine Dutertre, Ahad Khalilnezhad, Xiao Meng Zhang, Shawn Lim, Josephine Lum, Geraldine Koh, Charlene Foong, Pearly Jean Ai Yong, Kahbing Jasmine Tan, Reiko Sato, Kaori Tomari, Laurent Yvan-Charvet, Helen He, Emma Guttman-Yassky, Benoit Malleret, Rintaro Shibuya, Masashi Iwata, Baptiste Janela, Tsuyoshi Goto, Tan Siyun Lucinda, Mark B. Y. Tang, Colin Theng, Valerie Julia, Feriel Hacini-Rachinel, Kenji Kabashima, Florent Ginhoux
Summary: This study reveals the molecular characteristics of different macrophage and DC subsets in AD and PSO through single-cell analysis, identifying CD14(+) DC3 as a potential promoter of inflammation in PSO.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Sheena Suthen, Chun Jye Lim, Phuong H. D. Nguyen, Charles-Antoine Dutertre, Hannah L. H. Lai, Martin Wasser, Camillus Chua, Tony K. H. Lim, Wei Qiang Leow, Tracy Jiezhen Loh, Wei Keat Wan, Yin Huei Pang, Gwyneth Soon, Peng Chung Cheow, Juinn Huar Kam, Shridhar Iyer, Alfred Kow, Wai Leong Tam, Timothy W. H. Shuen, Han Chong Toh, Yock Young Dan, Glenn K. Bonney, Chung Yip Chan, Alexander Chung, Brian K. P. Goh, Weiwei Zhai, Florent Ginhoux, Pierce K. H. Chow, Salvatore Albani, Valerie Chew
Summary: This study analyzed the immune landscapes of hypoxic regions in hepatocellular carcinoma (HCC) and identified enriched immune subsets, including regulatory T cells, M2 macrophages, and HLA-DRlo cDC2, in hypoxia-high tumor regions. In contrast, hypoxia-low tumor regions showed an abundance of active granzyme B-hi PD-1(lo) CD8(+) T cells, indicating a relatively active immune landscape. The up-regulation of cancer-associated genes in tumor tissues and immunosuppressive genes in tumor-infiltrating leukocytes supported a highly pro-tumorigenic network in hypoxic HCC.
Editorial Material
Medicine, Research & Experimental
Jean-Luc Teillaud
M S-MEDECINE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Florian Ingelfinger, Lisa Ann Gerdes, Vladyslav Kavaka, Sinduya Krishnarajah, Ekaterina Friebel, Edoardo Galli, Pascale Zwicky, Reinhard Furrer, Christian Peukert, Charles-Antoine Dutertre, Klara Magdalena Eglseer, Florent Ginhoux, Andrea Flierl-Hecht, Tania Kumpfel, Donatella De Feo, Bettina Schreiner, Sarah Mundt, Martin Kerschensteiner, Reinhard Hohlfeld, Eduardo Beltran, Burkhard Becher
Summary: This study investigated the influence of genetic predisposition and environmental factors on the peripheral immune signatures in monozygotic twins discordant for multiple sclerosis (MS). Through data-driven computational tools and high-throughput single-cell technologies, the researchers identified an inflammatory shift in a specific group of immune cells in twins with MS, as well as the emergence of certain hyper-responsive immune cells. They found that the variance in CD25 expression by certain helper T cells with a naive phenotype was largely driven by genetic and shared early environmental influences. However, the expansion of helper T cells in twins with MS, which were also elevated in non-twin patients with MS, appeared to be independent of individual genetic makeup and correlated with disease severity.
Article
Multidisciplinary Sciences
Benoit Gamain, Carine Brousse, Nathan E. Rainey, Bere K. Diallo, Clara-Eva Paquereau, Alexandra Desrames, Jolita Ceputyte, Jean-Philippe Semblat, Olivier Bertrand, Stephane Gangnard, Jean-Luc Teillaud, Arnaud Chene
Summary: This study proposes a novel immunotherapeutic approach to redirect preexisting antibodies against EBV to target cells, which shows promising results in improving survival and achieving complete cancer remission in animal models.
Article
Hematology
Sahar Kassem, Bere K. Diallo, Nizar El-Murr, Nadege Carrie, Alexandre Tang, Alain Fournier, Helene Bonnevaux, Celine Nicolazzi, Marine Cuisinier, Isabelle Arnould, Sukhvinder S. Sidhu, Jill Corre, Herve Avet-Loiseau, Jean-Luc Teillaud, Helgi van de Velde, Dmitri Wiederschain, Marielle Chiron, Ludovic Martinet, Angela Virone-Oddos
Summary: This study compared the preclinical efficacy of SAR442085, a next-generation anti-CD38 monoclonal antibody (mAb), with first-generation anti-CD38 mAbs daratumumab and isatuximab. SAR442085 demonstrated higher binding affinity and better antibody-dependent cellular cytotoxicity (ADCC) against multiple myeloma (MM) cells compared to daratumumab and isatuximab. In addition, SAR442085 showed increased natural killer (NK) cell activation and degranulation against primary plasma cells, resulting in improved in vivo antitumor efficacy and survival. These findings support the evaluation of SAR442085 in phase I clinical development for patients with relapsed/refractory MM.
Editorial Material
Oncology
Jean-Lu Teillauo, Marie-Caroline Dieu-Nosjean
Summary: Increased plasma cell signatures are found to be predictive of extended overall survival in non-small-cell lung cancer patients treated with a PD-L1 inhibitor, and these cells are associated with the presence of tertiary lymphoid structures.
Article
Biochemistry & Molecular Biology
Rodrigo Nalio Ramos, Yoann Missolo-Koussou, Yohan Gerber-Ferder, Christian P. Bromley, Mattia Bugatti, Nicolas Gonzalo Nunez, Jimena Tosello Boari, Wilfrid Richer, Laurie Menger, Jordan Denizeau, Christine Sedlik, Pamela Caudana, Fiorella Kotsias, Leticia L. Niborski, Sophie Viel, Mylene Bohec, Sonia Lameiras, Sylvain Baulande, Laetitia Lesage, Andre Nicolas, Didier Meseure, Anne Vincent-Salomon, Fabien Reyal, Charles-Antoine Dutertre, Florent Ginhoux, Lene Vimeux, Emmanuel Donnadieu, Benedicte Buttard, Jerome Galon, Santiago Zelenay, William Vermi, Pierre Guermonprez, Eliane Piaggio, Julie Helft
Summary: This study identifies a specific population of FOLR2(+) tissue-resident macrophages in healthy mammary gland and breast cancer primary tumors, which interact with CD8(+) T cells and positively correlate with better patient survival.
Review
Immunology
Florent Ginhoux, Adam Yalin, Charles Antoine Dutertre, Ido Amit
Summary: The immune system is a complex, dynamic, and plastic ecosystem composed of multiple cell types. The advent of single-cell genomic approaches has revolutionized our knowledge of the cellular and molecular makeup of the immune system. Integration of multiomics at the single-cell level will pave the way for future advances in immunology research and clinical translation.
Article
Immunology
Aymeric Silvin, Stefan Uderhardt, Cecile Piot, Sandro Da Mesquita, Katharine Yang, Laufey Geirsdottir, Kevin Mulder, David Eyal, Zhaoyuan Liu, Cecile Bridlance, Morgane Sonia Thion, Xiao Meng Zhang, Wan Ting Kong, Marc Deloger, Vasco Fontes, Assaf Weiner, Rachel Ee, Regine Dress, Jing Wen Hang, Akhila Balachander, Svetoslav Chakarov, Benoit Malleret, Garett Dunsmore, Olivier Cexus, Jinmiao Chen, Sonia Garel, Charles Antoine Dutertre, Ido Amit, Jonathan Kipnis, Florent Ginhoux
Summary: Brain macrophage populations play important roles in brain development, homeostasis, aging pathogenesis, and neurodegeneration. However, the phenotypes, localization, and functions of these populations are not fully understood. This study systematically delineated brain macrophage populations using single-cell RNA sequencing integration in mice and identified two distinct cell lineages within the disease-associated microglia population. These findings provide insights into the heterogeneity of brain myeloid cells and offer potential cellular targets for the treatment of neurodegeneration.
Article
Biochemistry & Molecular Biology
Faezzah Baharom, Ramiro A. Ramirez-Valdez, Ahad Khalilnezhad, Shabnam Khalilnezhad, Marlon Dillon, Dalton Hermans, Sloane Fussell, Kennedy K. S. Tobin, Charles-Antoine Dutertre, Geoffrey M. Lynn, Soren Muller, Florent Ginhoux, Andrew S. Ishizuka, Robert A. Seder
Summary: Therapeutic cancer vaccines aim to enhance tumor-specific T cell immunity, but suppressive mechanisms within the tumor microenvironment can limit T cell function. This study investigated how different routes of vaccination impact intratumoral myeloid cells and found that intravenous administration of a nanoparticle vaccine induced tumor regression mediated by systemic type I interferon, leading to a reduction in intratumoral monocytes expressing immune-regulatory genes. In humans, these gene signatures are associated with worse outcomes. These results suggest that combining the generation of tumor-specific CD8+ T cells with remodeling of the tumor microenvironment holds promise for tumor immunotherapy.
Article
Immunology
Bjoern E. Clausen, Lukas Amon, Ronald A. Backer, Luciana Berod, Tobias Bopp, Anna Brand, Sven Burgdorf, Luxia Chen, Meihong Da, Ute Distler, Regine J. Dress, Diana Dudziak, Charles-Antoine Dutertre, Christina Eich, Anna Gabele, Melanie Geiger, Florent Ginhoux, Lucila Giusiano, Gloria J. Godoy, Ahmed E. Hamouda, Lukas Hatscher, Lukas Heger, Gordon F. Heidkamp, Lola C. Hernandez, Lukas Jacobi, Tomasz Kaszubowski, Wan Ting Kong, Christian H. K. Lehmann, Tamara Lopez-Lopez, Karsten Mahnke, Dominik Nitsche, Jorg Renkawitz, Rifat A. Reza, Pablo J. Saez, Laura Schlautmann, Madeleine T. Schmitt, Anna Seichter, Malte Sielaff, Tim Sparwasser, Patrizia Stoitzner, Giorgi Tchitashvili, Stefan Tenzer, Nounagnon R. Tochoedo, Damir Vurnek, Fabian Zink, Thomas Hieronymus
Summary: This article provides a collection of protocols for the functional characterization of mouse and human dendritic cells (DC), including endocytosis and metabolism analysis, transcriptomic and proteomic characterization, migration characterization, and measurement of inflammasome and antigen (cross)-presentation activity. These protocols, written by experienced scientists and peer-reviewed by leading experts, are essential resources for basic and clinical DC immunologists.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Akshamal M. Gamage, Wharton O. Y. Chan, Feng Zhu, Yan Ting Lim, Sandy Long, Matae Ahn, Chee Wah Tan, Randy Jee Hiang Foo, Wan Rong Sia, Xiao Fang Lim, Haopeng He, Weiwei Zhai, Danielle E. Anderson, Radoslaw Mikolaj Sobota, Charles-Antoine Dutertre, Lin-Fa Wang
Summary: Bats are reservoir hosts of zoonotic viruses with pandemic potential. This study utilized single-cell transcriptome sequencing to analyze the immune response in bat lungs upon infection with a double-stranded RNA virus. The study revealed the presence of neutrophils, NK cells, and T cells as the main immune cells in the lung tissue. Different subpopulations of CD8+ effector T cells and NK and T cells expressing genes involved in T cell activation and effector function were identified.
Article
Immunology
Egle Kvedaraite, Paul Milne, Ahad Khalilnezhad, Marion Chevrier, Raman Sethi, Hong Kai Lee, Daniel W. Hagey, Tatiana von Bahr Greenwood, Natalia Mouratidou, Martin Jadersten, Nicole Yee Shin Lee, Lara Minnerup, Yingrou Tan, Charles-Antoine Dutertre, Nathan Benac, You Yi Hwang, Josephine Lum, Amos Hong Pheng Loh, Jessica Jansson, Karen Wei Weng Teng, Shabnam Khalilnezhad, Weili Xu, Anastasia Resteu, Hong Liang Tey, Ng Lai Guan, Anis Larbi, Shanshan Wu Howland, Henrik Arnell, Samir E. L. Andaloussi, Jorge Braier, Georgios Rassidakis, Laura Galluzzo, Andrzej Dzionek, Jan-Inge Henter, Jinmiao Chen, Matthew Collin, Florent Ginhoux
Summary: This study used single-cell RNA-seq and protein analysis to dissect the heterogeneity of LCH cells and compare them with normal mononuclear phagocytes. The study found discriminatory signatures in LCH cells, indicating senescence and escape from immune surveillance. Additionally, the study uncovered two major lineages of LCH cells, DC2 and DC3/monocyte-like phenotypes.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Quentin Blampey, Nadege Bercovici, Charles-Antoine Dutertre, Isabelle Pic, Joana Mourato Ribeiro, Fabrice Andre, Paul-Henry Cournede
Summary: Cytometry technology allows for precise single-cell phenotyping within heterogeneous populations. However, traditional manual gating for cell type annotation lacks reproducibility and sensitivity to batch effect. In this study, we introduce Scyan, a novel Single-cell Cytometry Annotation Network that automatically annotates cell types using prior expert knowledge. We demonstrate that Scyan outperforms current state-of-the-art models on multiple public datasets and provides faster and interpretable results. Scyan also addresses complementary tasks such as batch-effect correction, debarcoding, and population discovery.
BRIEFINGS IN BIOINFORMATICS
(2023)
