Review
Cell Biology
Chunmei Fu, Li Zhou, Qing-Sheng Mi, Aimin Jiang
Summary: Although clinical trials of dendritic cell-based vaccines have been disappointing, recent studies have shown that cross-priming mediated by dendritic cells plays a critical role in generating anti-tumor immunity. This supports further development of dendritic cell vaccines as immunotherapy. Recent clinical studies have also shown promise with naturally circulating dendritic cells and dendritic cell-derived exosomes as cancer vaccines.
Review
Immunology
Sarah I. M. Sutherland, Xinsheng Ju, L. G. Horvath, Georgina J. Clark
Summary: Despite the success of using checkpoint inhibitors to reprim T cells to recognize tumors in certain malignancies, including melanoma, lung, and renal cell carcinoma, many tumors, such as prostate cancer, remain resistant to such treatment. DC-based immunotherapy, such as Sipuleucel-T, has shown improved overall survival in prostate cancer, but further research into DC vaccines has been limited. Understanding the immunosuppressive environment of prostate cancer and developing new vaccine strategies that can overcome this environment is essential for future success in immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Amelie Cachot, Mariia Bilous, Yen-Cheng Liu, Xiaokang Li, Margaux Saillard, Mara Cenerenti, Georg Alexander Rockinger, Tania Wyss, Philippe Guillaume, Julien Schmidt, Raphael Genolet, Giuseppe Ercolano, Maria Pia Protti, Walter Reith, Kalliopi Ioannidou, Laurence de Leval, Joseph A. Trapani, George Coukos, Alexandre Harari, Daniel E. Speiser, Alexander Mathis, David Gfeller, Hatice Altug, Pedro Romero, Camilla Jandus
Summary: CD4 T cells displaying cytotoxic phenotypes were identified in different human cancers through mining single-cell RNA-seq datasets. Ex vivo confirmation of the cytolytic tumor-specific CD4 T cells was achieved using peptide-MHCII-multimer technology. The cytotoxic activity of these cells, partially dependent on SLAMF7, was demonstrated to have delayed kinetics compared to classical cytotoxic lymphocytes, and agonistic engagement of SLAMF7 enhanced their cytotoxicity, indicating potential synergy with other cancer immunotherapies.
Article
Nanoscience & Nanotechnology
Chao Liu, Xue Liu, Xinchu Xiang, Xin Pang, Siyuan Chen, Yunming Zhang, En Ren, Lili Zhang, Xuan Liu, Peng Lv, Xiaoyong Wang, Wenxin Luo, Ningshao Xia, Xiaoyuan Chen, Gang Liu
Summary: This study presents a genetically engineered cell membrane nanovesicle for cancer immunotherapy. The nanovaccine, named ASPIRE, can improve antigen delivery to lymphoid organs and generate broad-spectrum T-cell responses that eliminate established tumors. This work provides a powerful vaccine formula that can directly activate both native T cells and exhausted T cells, suggesting a general strategy for personalized cancer immunotherapy.
NATURE NANOTECHNOLOGY
(2022)
Article
Oncology
Nana Dang, Yuan Lin, Mark Waer, Ben Sprangers
Summary: Alloantibodies, particularly immunoglobulin G (allo-IgG), enhance rejection of tumors sharing the same major histocompatibility complex (MHC) in mice. In this study, high titer allo-IgG generated through immunization increased tumor immunogenicity, leading to a systemic antitumor response when combined with 5-fluorouracil. The tumor-specific response relied on the lymph nodes, suggesting a potential use of allo-IgG in cancer treatment.
Review
Biochemistry & Molecular Biology
Reza Hosseini, Leila Asef-Kabiri, Hassan Yousefi, Hamzeh Sarvnaz, Majid Salehi, Mohammad Esmaeil Akbari, Nahid Eskandari
Summary: This paper delves into the impact of tumor-derived exosomes on dendritic cells and how they induce subversion of DCs differentiation, maturation, and function, as well as their significance at the therapeutic level. Understanding the exosomal content and pathways responsible for immune evasion could lead to the development of novel therapeutic approaches.
Article
Immunology
Elias A. T. Koch, Niels Schaft, Mirko Kummer, Carola Berking, Gerold Schuler, Kenichiro Hasumi, Jan Doerrie, Beatrice Schuler-Thurner
Summary: Uveal melanoma is a rare disease with poor response to traditional therapies. Researchers designed a trial using personalized dendritic cell vaccines to activate the immune system and potentially improve clinical outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Hinda Najem, Anantha Marisetty, Craig Horbinski, James Long, Jason T. Huse, Isabella C. Glitza Oliva, Sherise D. Ferguson, Priya U. Kumthekar, Derek A. Wainwright, Peiwen Chen, Maciej S. Lesniak, Jared K. Burks, Amy B. Heimberger
Summary: The TME of LMD lacks CD3+ T cells but is enriched in immune suppression and innate immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Oncology
Yasuyuki Saito, Satomi Komori, Takenori Kotani, Yoji Murata, Takashi Matozaki
Summary: This review outlines the role of type-2 conventional dendritic cells (cDC2s) in antitumor immunity and summarizes the latest progress in cancer vaccination and cDC2-targeted cancer immunotherapy.
Article
Oncology
Adrien Joseph, Pan Juncheng, Michele Mondini, Nizar Labaied, Mauro Loi, Julien Adam, Antoine Lafarge, Valentina Astesana, Florine Obrist, Christophe Klein, Norma Bloy, Gautier Stoll, Nicolas Signolle, Catherine Genestie, Diane Damotte, Marco Alifano, Alexandra Leary, Patricia Pautier, Philippe Morice, Sebastien Gouy, Eric Deutsch, Cyrus Chargari, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Judith Michels, Guido Kroemer, Maria Castedo
Summary: Tumors adapt their metabolism to resist therapeutic interventions like cisplatin, affecting the local immunosurveillance. This study found that PDXK and PAR levels impact the response to cisplatin, providing new insights into therapeutic failures in cancer treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Feng Shan, Ashwin Somasundaram, Tullia C. Bruno, Creg J. Workman, Dario A. A. Vignali
Summary: The success of immunotherapy in oncology highlights the important role of the immune system in cancer development. Regulatory T cells (Tregs) play multiple roles in the tumor microenvironment, particularly in suppressing T cell activation. Understanding the subpopulations of Tregs and their functions within the complex networks of the tumor microenvironment is crucial for the development of next-generation immunotherapies.
Article
Chemistry, Multidisciplinary
Li Ding, Qingqing Gao, Zhuobin Xu, Liangliang Cai, Sujuan Chen, Xinyue Zhang, Peng Cao, Gang Chen
Summary: An NK cell-mediated Ad delivery system has been developed for combinational immunotherapy and virotherapy of cancer, which not only enhances antitumor immunity but also relieves immunosuppression in the tumor microenvironment. In vitro and in vivo data demonstrate the excellent antitumor and antimetastatic functions of the Ad@NK system by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME.
Article
Virology
Ida Uddback, Jacob E. Kohlmeier, Allan R. Thomsen, Jan P. Christensen
Summary: Understanding the complexity of T-cell epitope hierarchy in humans using mouse models is challenging. Investigating immune response to influenza virus infection in only one mouse strain, C57BL/6, limits our understanding. In this study, immunization with an adenoviral vector encoding influenza A virus polymerase acidic (AdIiPA) protein induced a high number of PA-specific T cells in C57BL/6 mice but provided only partial protection upon challenge. Immunization of BALB/c mice with AdIiPA, however, resulted in full protection, dependent on CD8 T cells, and identified a novel H-2D(d)-restricted epitope (PA33). These findings offer a new tool to study PA-specific immunity in mice with an H-2(d) haplotype, and highlight the importance of evaluating limitations of using a single mouse strain in vaccine studies.
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)
Review
Medicine, Research & Experimental
Feyza Gul Ozbay Kurt, Samantha Lasser, Ihor Arkhypov, Jochen Utikal, Viktor Umansky
Summary: Despite the success of immune checkpoint inhibitors in melanoma treatment, resistance to them remains a challenge. Myeloid-derived suppressor cells play a crucial role in ICI resistance and creating an immunosuppressive tumor microenvironment. Targeting MDSCs is considered a promising strategy to improve melanoma immunotherapy, and this review discusses the mechanism, studies, and potential strategies for inhibiting MDSC functions.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Sophia M. Loick, Anne Froehlich, Jennis Gabrielpillai, Alina Franzen, Timo J. Vogt, Joern Dietrich, Constanze Wiek, Kathrin Scheckenbach, Sebastian Strieth, Jennifer Landsberg, Dimo Dietrich
Summary: This study investigated DNA methylation of TNFRSF4 (OX40) and TNFRSF18 (GITR, AITR) genes in head and neck squamous cell carcinomas, aiming to understand their regulation and potential as biomarkers for immunotherapy. The results revealed a complex methylation pattern and significant associations with gene activity, HPV infection, immune cell infiltrates, interferon-gamma signature, and overall survival. The study provides a framework for testing specific CpG sites as predictive biomarkers in immunotherapies.
JOURNAL OF IMMUNOTHERAPY
(2022)
Article
Oncology
Ahmad A. Tarhini, Sandra J. Lee, Aik-Choon Tan, Issam M. El Naqa, F. Stephen Hodi, Lisa H. Butterfield, William A. LaFramboise, Walter J. Storkus, Arivarasan D. Karunamurthy, Jose R. Conejo-Garcia, Patrick Hwu, Howard Streicher, Vernon K. Sondak, John M. Kirkwood
Summary: Melanoma of unknown primary (MUP) has a significantly better prognosis and shows evidence of significantly enhanced immune activation within the tumor microenvironment and the circulation in high-risk melanoma patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Dennis Niebel, Anne Froehlich, Romina Zarbl, Simon Fietz, Luka de Vos, Timo J. Vogt, Joern Dietrich, Judith Sirokay, Pia Kuster, Gonzalo Saavedra, Susana Ramirez Valladolid, Friederike Hoffmann, Sebastian Strieth, Jennifer Landsberg, Dimo Dietrich
Summary: Our study demonstrates the epigenetic regulation of TIGIT expression through DNA methylation within the melanoma microenvironment. TIGIT DNA methylation and expression may serve as predictive biomarkers in the context of immunotherapies in melanoma.
CLINICAL EPIGENETICS
(2022)
Article
Immunology
Bratislav M. Janjic, Aditi Kulkarni, Robert L. Ferris, Lazar Vujanovic, Nikola L. Vujanovic
Summary: Research has found that circulating B cells play a role in mediating the immune mechanism against cancer, inducing apoptosis and efficiently killing leukemia and solid tumor cells. This is achieved through the simultaneous activation of multiple plasma membrane-associated TNF superfamily (TNFSF) ligands expressed by B cells. B cells from cancer patients express lower levels of TNFSF ligands, resulting in weaker cytotoxic activity.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Immunology
Janin Chandra, Morten Hansen, Nathalie Labarriere, Ilaria Marigo, Fernando Souza-Fonseca-Guimaraes, Lazar Vujanovic, Yoshinobu Koguchi, Nicolas Jacquelot
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Luka de Vos, Tzaitel Maria Carrillo Cano, Romina Zarbl, Niklas Kluemper, Damian Johannes Ralser, Alina Franzen, Emmanuelle Herr, Jennis Gabrielpillai, Timo Jakob Vogt, Joern Dietrich, Sebastian Strieth, Jennifer Landsberg, Dimo Dietrich
Summary: This study comprehensively analyzed the DNA methylation status of immune checkpoint genes in uveal melanoma (UM), and found that the methylation of these genes was strongly associated with mRNA expression, BAP1 aberrancy, and patients' survival. These findings indicate the epigenetic regulation of immune checkpoints through DNA methylation in UM, highlighting the prognostic significance of DNA methylation in these genes and providing a rationale for using methylation testing as predictive biomarkers for immunotherapy response.
JOURNAL OF IMMUNOTHERAPY
(2022)
Article
Oncology
Tobias Schatton, Yuta Itoh, Christina Martins, Erik Rasbach, Praveen Singh, Mariana Silva, Kyla Mucciarone, Markus V. Heppt, Jenna Geddes-Sweeney, Kate Stewart, Anne Brandenburg, Jennifer Liang, Charles J. Dimitroff, Martin C. Mihm, Jennifer Landsberg, Christoph Schlapbach, Christine G. Lian, George F. Murphy, Thomas S. Kupper, Matthew R. Ramsey, Steven R. Barthel
Summary: Tim-3 is an intrinsic growth-suppressive receptor in melanoma cells, and blocking it may promote MAPK-dependent tumorigenesis, counteracting the antitumor activity of T-cell-directed Tim-3 inhibition.
Article
Multidisciplinary Sciences
Juraj Adamik, Paul Munson, Felix J. Hartmann, Alexis J. Combes, Philippe Pierre, Matthew F. Krummel, Sean C. Bendall, Rafael J. Arguello, Lisa H. Butterfield
Summary: Assessing metabolic activity at the single-cell level provides important insights into the immune profiles of human dendritic cells. This study reveals the metabolic differences between immune stimulatory and tolerogenic dendritic cells, and highlights the simultaneous engagement of multiple metabolic pathways in distinct stages of dendritic cell differentiation.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Philipp Jansen, Adelaida Creosteanu, Viktor Matyas, Amrei Dilling, Ana Pina, Andrea Saggini, Tobias Schimming, Jennifer Landsberg, Birte Burgdorf, Sylvia Giaquinta, Hansgeorg Mueller, Michael Emberger, Christian Rose, Lutz Schmitz, Cyrill Geraud, Dirk Schadendorf, Joerg Schaller, Maximilian Alber, Frederick Klauschen, Klaus G. Griewank
Summary: In this study, a machine learning algorithm was used to detect fungal elements on digitized histologic sections of human nail specimens, and its performance was compared with that of dermatopathologists. The results demonstrated that the algorithm achieved a comparable sensitivity to the human pathologists. This finding suggests that machine learning algorithms can serve as supportive diagnostic tools to improve the screening efficiency of fungal infections.
Article
Oncology
Xiaoyu Li, Jingjing Li, Yue Zheng, Sandra J. Lee, Jun Zhou, Anita Giobbie-Hurder, Lisa H. Butterfield, Glenn Dranoff, F. Stephen Hodi
Summary: With the successful development of immune checkpoint blockade, the addition of granulocyte-macrophage-CSF (GM-CSF) has been shown to improve efficacy and decrease adverse events. The presence of ICOS+CD4+ or ICOS+CD8+ T cells in the peripheral blood is significantly higher in patients treated with ipilimumab plus GM-CSF compared to those treated with ipilimumab alone. Soluble ICOS splice variants have suppressive effects and can serve as a biomarker for GM-CSF and immune checkpoint blockade-based therapies.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Oncology
Damian J. Ralser, Emmanuelle Herr, Luka de Vos, Zsofi Kulcsar, Romina Zarbl, Niklas Kluemper, Gerrit H. Gielen, Alexander Philippe Maas, Friederike Hoffmann, Joern Dietrich, Pia Kuster, Alexander Mustea, Nicole Glodde, Glen Kristiansen, Sebastian Strieth, Jennifer Landsberg, Dimo Dietrich
Summary: In this study, the epigenetic regulation of ICOS in melanoma by DNA methylation was investigated. High ICOS mRNA expression was associated with enriched immune cell infiltration and favorable overall survival in non-ICB-treated patients. ICOS hypomethylation correlated with poor overall survival in non-ICB patients but predicted higher response and prolonged survival in ICB-treated patients. The study also revealed cytoplasmic and sporadic nuclear tumor cell-intrinsic ICOS protein expression, which could be induced by pharmacological demethylation with decitabine.
BIOMARKER RESEARCH
(2023)
Review
Oncology
Ayana T. Ruffin, Housaiyin Li, Lazar Vujanovic, Dan P. Zandberg, Robert L. Ferris, Tullia C. Bruno
Summary: Targeted immunotherapy has improved survival in head and neck squamous cell carcinoma (HNSCC), but new immunotherapies considering the entire HNSCC tumour microenvironment are needed to enhance T cell responses. Recent advancements have provided a comprehensive understanding of the cellular constituents and interactions within the complex HNSCC microenvironment.
NATURE REVIEWS CANCER
(2023)
Review
Immunology
Lisa H. Butterfield, Yana G. Najjar
Summary: The approval of immune checkpoint inhibitors has shifted the treatment paradigm for malignancies. Combination therapies and biomarker studies are important for maximizing clinical efficacy.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Juraj Adamik, Paul V. Munson, Deena M. Maurer, Felix J. Hartmann, Sean C. Bendall, Rafael J. Arguello, Lisa H. Butterfield
Summary: This study analyzed the transcriptomic and immune-metabolic profiles of dendritic cells (DCs) from patients with late-stage melanoma. The results suggest that the metabolic profile of DCs is associated with the immunostimulatory potential of cancer vaccines.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Jenny Bischoff, Charlotte Fries, Alexander Heer, Friederike Hoffmann, Carsten Meyer, Jennifer Landsberg, Wiebke K. Fenske
Summary: This study reports on different endocrine immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitors (ICI) and highlights new-onset hyponatremia as a potential early biomarker for irAEs.
JOURNAL OF THE ENDOCRINE SOCIETY
(2022)