Article
Oncology
Bas D. Koster, Marta Lopez Gonzalez, Mari Fcm van den Hout, Annelies W. Turksma, Berbel J. R. Sluijter, Barbara G. Molenkamp, Paul A. M. van Leeuwen, Saskia Vosslamber, Rik J. Scheper, Alfons J. M. van den Eertwegh, M. Petrousjka van den Tol, Ekaterina J. Jordanova, Tanja D. de Gruijl
Summary: Injection of CpG-B at the primary tumor excision site prior to re-excision and sentinel node biopsy leads to increased recruitment and activation of antigen-presenting cell (APC) subsets in the skin, particularly CD83(+), CD14(+), CD68(+), and CD123(+) APC in the reticular dermis. This recruitment is correlated with T cell infiltration, specifically with cDC1 and CD14(+) APC counts. These findings suggest a role for CpG-induced cDC1 and CD14(+) APC activation in promoting T cell infiltration through CXCL10 release.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Conor M. Henry, Carlos A. Castellanos, Caetano Reis E. Sousa
Summary: In this review, the role of dendritic cell natural killer group receptor-1 (DNGR-1) in cDC1 and its functions in anti-viral and anti-tumor immunity are discussed. The study found that DNGR-1 can promote inducible rupture of phagocytic or endocytic compartments containing dead cell debris, making dead cell-associated antigens accessible to cDC1. Additionally, DNGR-1 can recognize dead cells and participate in immune response. Therefore, the study of DNGR-1 has opened new perspectives into cross-presentation, which may have applications in immunotherapy of cancer and vaccination against viral diseases.
SEMINARS IN IMMUNOLOGY
(2023)
Review
Oncology
Francisco J. Cueto, David Sancho
Summary: Current cancer immunotherapy efforts focus on enhancing T cell effector function, but stimulating dendritic cells (DCs) may improve treatment outcomes. Specifically, utilizing the Flt3/Flt3L axis to boost DC function shows promising potential for cancer immunotherapy.
Article
Oncology
Stephen T. Ferris, Ray A. Ohara, Feiya Ou, Renee Wu, Xiao Huang, Sunkyung Kim, Jing Chen, Tian-Tian Liu, Robert D. Schreiber, Theresa L. Murphy, Kenneth M. Murphy
Summary: It has been found that dendritic cells (DC) do not directly activate tumor-specific T cells, but induce anti-tumor immune responses by transferring their antigens to host DCs. Type 1 conventional DCs (cDC1) are more effective than GMDC as cancer vaccines. Vaccination with cDC1 can activate tumor-specific CD8+ T cells and lead to tumor rejection.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Yoke Seng Lee, Liam J. O'Brien, Carina M. Walpole, Frances E. Pearson, Ingrid M. Leal-Rojas, Kelly-Anne Masterman, Victoria Atkinson, Andrew Barbour, Kristen J. Radford
Summary: The study found that the number of CD141(+) dendritic cells in the blood of melanoma patients was significantly reduced, and these cells exhibited impaired function after peripheral stimulation. In non-responding patients, the number and function of these cells continued to decline during treatment. Indirectly expanding and activating CD141(+) dendritic cells in vivo with Flt3L and a TLR3 agonist can enhance the efficacy of anti-PD-1 treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Medicine, Research & Experimental
Shanshan Gou, Shuai Wang, Wenwen Liu, Guanyu Chen, Dongyang Zhang, Jiangfeng Du, Zhongyi Yan, Hongfei Wang, Wenjie Zhai, Xinghua Sui, Yahong Wu, Yuanming Qi, Yanfeng Gao
Summary: CBP-12 has been developed as an adjuvant-free peptide vaccine carrier for cancer immunotherapy, showing enhanced uptake and cross-presentation of antigens, leading to strong CD8(+) T cell responses and antitumor effects even in adjuvant-free conditions.
Article
Biotechnology & Applied Microbiology
M. H. Lahoud, K. J. Radford
Summary: DC vaccines are safe and effective in inducing tumor immune responses, with recent advances in targeting CLEC9A antibodies showing promise for developing vaccines for infectious diseases and cancer. The development of human CLEC9A antibodies now paves the way for their application in cancer immunotherapy.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2022)
Review
Medicine, Research & Experimental
Zhanbo Sun, Lingyun Zhang, Lixian Liu
Summary: This article summarizes the lipid metabolism of dendritic cells (DCs) under physiological conditions, analyzes the role of reprogramming the lipid metabolism of DCs in tumor immune regulation, and discusses potential immunotherapeutic strategies.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Emile J. Clappaert, Daliya Kancheva, Jan Brughmans, Ayla Debraekeleer, Pauline M. R. Bardet, Yvon Elkrim, Dagmar Lacroix, Maida Zivalj, Ahmed E. I. Hamouda, Jo A. Van Ginderachter, Sofie Deschoemaeker, Damya Laoui
Summary: This study found that while Flt3L treatment can increase all cDC subsets in the tumor, it does not reduce tumor growth in any of the models. In addition, in some cases, Flt3L treatment also leads to an increase in CD81(+)migcDC1 subset, which has Treg-inducing potential. Overall, increasing cDC numbers in the tumor alone may not improve anti-tumor responses and may not be beneficial for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biotechnology & Applied Microbiology
Phillip Johnson, Nikita Rosendahl, Kristen J. Radford
Summary: Targeting cDC1 as a therapeutic option in cancer vaccines holds potential in improving tumor immunogenicity. Manipulation of cDC1 quantity and quality shows promise in enhancing the immune response in cancer patients. New technologies are advancing rapidly in understanding and generating cDC1 in vitro for clinical translation.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Review
Biology
Peng Liu, Liwei Zhao, Guido Kroemer, Oliver Kepp
Summary: This review summarizes the importance of dendritic cells, particularly conventional type 1 dendritic cells (cDC1), in anti-tumor immunity and their potential applications in immunotherapy.
Article
Oncology
Philippa Meiser, Moritz A. Knolle, Anna Hirschberger, Gustavo P. de Almeida, Felix Bayerl, Sebastian Lacher, Anna-Marie Pedde, Sophie Flommersfeld, Julian Hoenninger, Leonhard Stark, Fabian Stoegbauer, Martina Anton, Markus Wirth, Dirk Wohlleber, Katja Steiger, Veit R. Buchholz, Barbara Wollenberg, Christina E. Zielinski, Rickmer Braren, Daniel Rueckert, Percy A. Knolle, Georgios Kaissis, Jan P. Boettcher
Summary: A study found that the clustering of immune cells within tumors, orchestrated by a specific type of immune cell called cDC1, is a unique feature associated with effective anti-cancer immunity. These clusters promote the activation and expansion of stem-like CD8+ T cells, which play a crucial role in cancer immune control. This finding has important implications for cancer therapy.
Article
Oncology
Anastasia Prokopi, Christoph H. Tripp, Bart Tummers, Florian Hornsteiner, Sarah Spoeck, Jeremy Chase Crawford, Derek R. Clements, Mirjana Efremova, Katharina Hutter, Lydia Bellmann, Giuseppe Cappellano, Bruno L. Cadilha, Sebastian Kobold, Louis Boon, Daniela Ortner, Zlatko Trajanoski, Suzie Chen, Tanja D. de Gruijl, Juliana Idoyaga, Douglas R. Green, Patrizia Stoitzner
Summary: Immunotherapy with checkpoint inhibitors has shown impressive results in patients with melanoma, but many still do not benefit from this treatment due to factors such as lack of tumor-infiltrating T cells and loss of intratumoral dendritic cells. In a melanoma mouse model, researchers found that tumor progression is characterized by upregulation of checkpoint molecules and gradual loss of dermal conventional DC 2 subset. Monotherapy with checkpoint blockade was not effective, but boosting DC numbers and activation increased tumor immunogenicity, leading to improved T cell function and delayed tumor growth when combined with antibodies against PD-1 and TIM-3. The study highlights the importance of skin DC in cancer immunotherapy and suggests that restoring DC function is key to enhancing tumor immunogenicity and responsiveness to checkpoint blockade therapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Titi Chen, Qi Cao, Ruifeng Wang, Guoping Zheng, Farhana Azmi, Jeffery Wang, Vincent W. Lee, Yuan Min Wang, Hong Yu, Manish Patel, Chow Heok P'ng, Stephen Alexander, Natasha M. Rogers, Yiping Wang, David C. H. Harris
Summary: In human kidney diseases, cDC1 numbers significantly increase in acute tubular necrosis and proliferative glomerulonephritis, mainly located in the interstitium but also in the glomeruli in certain conditions. The number of cDC1s correlates with disease severity, pathological features, and prognosis, while also showing an association with CD8(+) T cell numbers in lupus nephritis and pauci-immune GN.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Yuan Zhuang, Xiaomei Zhao, Baoying Yuan, Zhaochong Zeng, Yixing Chen
Summary: The study showed that the CCR5 antagonist MVC can induce macrophage polarization towards the M1 phenotype by blocking the CCL5-CCR5 signaling pathway, thereby enhancing the sensitivity and apoptosis of human hepatoma cells to radiation.
JOURNAL OF HEPATOCELLULAR CARCINOMA
(2021)
Review
Immunology
Ana Redondo-Urzainqui, Elena Hernandez-Garcia, Emma Clare Laura Cook, Salvador Iborra
Summary: This review summarizes the role of dendritic cells (DCs) in chronic metabolic inflammation and their function in maintaining metabolic tissue homeostasis.
IMMUNOLOGY LETTERS
(2023)
Review
Oncology
Ignacio Melero, Miguel F. Sanmamed, Javier Glez-Vaz, Carlos Luri-Rey, Jun Wang, Lieping Chen
Summary: Twenty-five years ago, it was discovered that agonist anti-CD137 monoclonal antibodies enhanced CD8+ T-cell antitumor immunity and effectively eradicated transplanted mouse tumors. Despite causing severe liver inflammation in some patients, the agonist antibody urelumab showed evidence of activity against melanoma and non-Hodgkin lymphoma. CD137's signaling domain has been incorporated into chimeric antigen receptors, improving their efficacy. New CD137 agonists, primarily based on bispecific constructs, are currently being tested in early-phase trials and are showing promising safety and clinical activity.
Letter
Cardiac & Cardiovascular Systems
Esther Aix, Alex Gallinat, Carla Yago-Diez, Javier Lucas, Manuel Jose Gomez, Alberto Benguria, Patricia Freitag, Elizabeth Cortez-Toledo, Laura Fernandez de Manuel, Lucia Garcia-Cuasimodo, Hector Sanchez-Iranzo, Maria C. Montoya, Ana Dopazo, Fatima Sanchez-Cabo, Nadia Mercader, Javier E. Lopez, Bernd K. Fleischmann, Michael Hesse, Ignacio Flores
Article
Biology
Maria-Bernadette Madel, Julia Halper, Lidia Ibanez, Lozano Claire, Matthieu Rouleau, Antoine Boutin, Adrien Mahler, Rodolphe Pontier-Bres, Thomas Ciucci, Majlinda Topi, Christophe Hue, Jerome Amiaud, Salvador Iborra, David Sancho, Dominique Heymann, Henri-Jean Garchon, Dorota Czerucka, Florence Apparailly, Isabelle Duroux-Richard, Abdelilah Wakkach, Claudine Blin-Wakkach
Summary: This study explores the specific traits of inflammatory and steady-state osteoclasts using transcriptomic profiling, differentiation assays, and in vivo analysis in mice. The authors identify and validate pattern-recognition receptors (PRR) Tlr2, Dectin-1, and Mincle as major regulators of inflammatory osteoclasts. They demonstrate that the administration of the yeast probiotic Saccharomyces boulardii CNCM I-745 (Sb) reduces bone loss in ovariectomized mice by regulating the inflammatory environment and inhibiting inflammatory osteoclastogenesis. The study also shows that Sb derivatives and agonists of Tlr2, Dectin-1, and Mincle specifically inhibit the differentiation of inflammatory osteoclasts in vitro. These findings have important implications for the development of therapeutic strategies for inflammatory bone loss.
Article
Cardiac & Cardiovascular Systems
Joaquim Grego-Bessa, Paula Gomez-Apinaniz, Belen Prados, Manuel Jose Gomez, Donal MacGrogan, Jose Luis de la Pompa
Summary: This study investigated the functions and downstream mechanisms of Nrg1 signaling during ventricular chamber development. The Nrg1-ErbB2/ErbB4-Erk axis was found to be a crucial regulator of cardiomyocyte cell cycle progression and migration.
CIRCULATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Diego Calzada-Fraile, Salvador Iborra, Marta Ramirez-Huesca, Inmaculada Jorge, Enrico Dotta, Elena Hernandez-Garcia, Noa Martin-Cofreces, Estanislao Nistal-Villan, Esteban Veiga, Jesus Vazquez, Giulia Pasqual, Francisco Sanchez-Madrid
Summary: Antigen presentation induces upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs, mediating DC licensing. Adoptive transfer of psDC enhances pathogen-specific CD8(+) T cell responses and protects mice from infection. The study reveals crucial molecular events underlying psDC licensing.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Assunta Cirella, Elixabet Bolanos, Carlos Luri-Rey, Claudia Augusta Di Trani, Irene Olivera, Gabriel Gomis, Javier Glez-Vaz, Beatrice Pinci, Saray Garasa, Sandra Sanchez-Gregorio, Arantza Azpilikueta, Inaki Eguren-Santamaria, Karmele Valencia, Belen Palencia, Maite Alvarez, Maria C. Ochoa, Alvaro Teijeira, Pedro Berraondo, Ignacio Melero
Summary: Intratumoral immunotherapy strategies for cancer based on IL-12 encoding cDNA and mRNA combined with anti-PD-(L)1 monoclonal antibodies are being developed. Chimeric mRNAs encoding single-chain IL-12 fused to scFv antibodies binding to TGF-b and CD137 have been constructed. Efficacy was observed in mouse cancer models following mRNA intratumoral injections, and distant effects on untreated lesions were increased when combined with systemic PD-1 blockade.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Multidisciplinary Sciences
Javier Glez-Vaz, Arantza Azpilikueta, Maria C. Ochoa, Irene Olivera, Gabriel Gomis, Asunta Cirella, Carlos Luri-Rey, Maite alvarez, Jose. L. L. Perez-Gracia, Sergio Ciordia, Inaki Eguren-Santamaria, Raluca Alexandru, Pedro Berraondo, Carlos de Andrea, Alvaro Teijeira, Fernando Corrales, Juan. M. M. Zapata, Ignacio Melero
Summary: CD137 is a member of the TNFR family that mediates potent T cell costimulatory signals upon ligation by CD137L or agonist monoclonal antibodies (mAbs). The physical association between cIAP1/cIAP2 and the CD137 signaling complex is demonstrated. cIAPs are required for CD137 signaling towards NF-κB and MAPK pathways, and for the costimulation of human and mouse T lymphocytes.
Article
Oncology
Angela Bella, Leire Arrizabalaga, Claudia Augusta Di Trani, Jose Gonzalez-Gomariz, Celia Gomar, Joan Salvador Russo-Cabrera, Irene Olivera, Assunta Cirella, Myriam Fernandez-Sendin, Maite Alvarez, Alvaro Teijeira, Cigdem Atay, Jose Medina-Echeverz, Maria Hinterberger, Hubertus Hochrein, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: Intraperitoneal administration of MVA vectors encoding scIL-12 can stimulate immune response mediated by tumor-specific CD8+ T lymphocytes and effectively inhibit tumor growth in the peritoneal cavity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Meeting Abstract
Oncology
Eneko Garate-Soraluze, Irantzu Serrano-Mendioroz, Carlos E. de Andrea, Toni Rullan, Christina Claus, Pablo Umana, Christian klein, Ignacio Melero, Maria E. Rodriguez-Ruiz
Meeting Abstract
Oncology
Javier Glez-Vaz, Arantza Azpilikueta, Maria Carmen Ochoa, Irene Olivera, Gabriel Gomis, Asunta Cirella, Carlos Luri-Rey, Maite Alvarez, Sergio Ciordia, Pedro Berraondo, Alvaro Teijeira, Fernando Corrales, Juan M. Zapata, Ignacio Melero
Meeting Abstract
Oncology
Angela Bella, Leire Arrizabalaga, Claudia Augusta Di Trani, Jose Gonzalez-Gomariz, Assunta Cirella, Irene Olivera, Maite Alvarez, Alvaro Teijeira, Cigdem Atay Langbein, Jose Medina-Echeverz, Maria Hinterberger, Hubertus Hochrein, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Meeting Abstract
Oncology
Maite Alvarez, Maria C. Ochoa, Carmen Molina, Alvaro Teijeira, Saray Garasa, Sandra Sanchez-Gregorio, Irene Olivera, Javier Glez-Vaz, Asunta Cirella, Gabriel Gomis, Jose Gonzalez-Gomariz, Pedro Berraondo, Ignacio Melero
Article
Biochemistry & Molecular Biology
Michel Enamorado, Warakorn Kulalert, Seong-Ji Han, Indira Rao, Jeremie Delaleu, Verena M. Link, Daniel Yong, Margery Smelkinson, Louis Gil, Saeko Nakajima, Jonathan L. Linehan, Nicolas Bouladoux, Josette Wlaschin, Juraj Kabat, Olena Kamenyeva, Liwen Deng, Inta Gribonika, Alexander T. Chesler, Isaac M. Chiu, Claire E. Le Pichon, Yasmine Belkaid
Summary: Tissue immunity and responses to injury rely on coordinated action and communication among physiological systems. The study demonstrates that adaptive responses to the microbiota can directly promote sensory neuron regeneration after injury. The researchers found that commensal-specific T cells in the skin tissue express neuronal interaction and repair genes, promoting axon growth and local nerve regeneration. The cytokine IL-17A released by these T cells signals to sensory neurons, indicating its importance in the process.
Article
Hematology
Maria Piedad Menendez-Gutierrez, Jesus Porcuna, Ramesh Nayadk, Ana Paredes, Haixia Niu, Vanessa Nunez, Aditi Paranjpe, Manuel J. Gomez, Anukana Bhattacharjee, Daniel J. Schnell, Fatima Sanchez-Cabo, John S. Welch, Nathan Salomonis, Jose A. Cancelas, Mercedes Ricote
Summary: Hematopoietic stem cells (HSCs) maintain hematopoietic fitness by balancing self-renewal and differentiation, with retinoid X receptor (RXR) family transcription factors regulating HSC quiescence. Dual deficiency of hematopoietic RXR alpha and RXR beta leads to HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXR alpha and RXR beta maintain HSC quiescence, survival, and chromatin compaction, and their deficiency causes transcriptome changes and premature acquisition of an aging-like HSC signature in HSCs. Myc haploinsufficiency prevents fitness loss and transcriptome/splicing alterations in RXR alpha;RXR beta-deficient HSCs. This study highlights the critical importance of RXRs in maintaining HSC fitness and preventing premature aging.