Article
Medicine, Research & Experimental
Shaokui Chen, Ruixin Li, Yibo Chen, Chon-Kit Chou, Zhexuan Zhang, Yang Yang, Ping Liao, Qingqing Wang, Xin Chen
Summary: This study found that scutellarin, a Chinese herbal extract, can enhance the efficacy of tumor immunotherapy by disrupting the TNF-TNFR2 interaction. Scutellarin inhibits the proliferation of tumor-associated regulatory T cells, leading to increased infiltration of anti-tumor T cells in the tumor.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Immunology
Xuguang Tai, Alyssa Indart, Mirelle Rojano, Jie Guo, Nicolai Apenes, Tejas Kadakia, Marco Craveiro, Amala Alag, Ruth Etzensperger, Mohamed Elsherif Badr, Flora Zhang, Zhongmei Zhang, Jie Mu, Terry Guinter, Assiatu Crossman, Larry Granger, Susan Sharrow, Xuyu Zhou, Alfred Singer
Summary: Singer and colleagues have found that the fate of autoreactive CD4(+) thymocytes is determined by the timing and duration of agonist signaling. Early agonist signaling leads to clonal deletion, while late agonist signaling induces the differentiation into Foxp3(+) T-reg cells or IL-2(+) T-eff cells depending on TGF-beta's interference with TCR signaling. These findings reveal that disruption or persistence of agonist signaling is a general mechanism that determines the lineage fate of autoreactive thymocytes in the thymus.
Article
Oncology
Ping Li, Fengyang Chen, Jingbin Zheng, Yang Yang, Yuan Li, Yifei Wang, Xin Chen
Summary: Cyclophosphamide can abrogate the effects of bleomycin on the expansion of Tregs, and the combination therapy of these two chemotherapeutic agents shows synergistic anti-tumor effects in cancer treatment.
CANCER BIOLOGY & MEDICINE
(2021)
Review
Immunology
Nikolaos Skartsis, Leonardo M. R. Ferreira, Qizhi Tang
Summary: TNFa blocking agents, the first-in-class biologic drugs used for treating autoimmune diseases, have shown paradoxical exacerbation of autoimmunity in some patients. The complex signaling pathways of TNFa might explain the controversial findings of previous studies. Targeted manipulation of TNFa-TNF receptor signaling on select CD4(+) T cell subsets may offer specific therapeutic interventions for autoimmune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Christina Seitz, Anne-Laure Joly, Fang Fang, Katie Frith, Paul Gray, John Andersson
Summary: The transcription factor FOXP3 is crucial for the development and function of CD4(+)FOXP3(+) regulatory T (Treg) cells. Alterations in the expression of FOXP3 isoforms are associated with inflammatory disease progression. This study investigates the effects of a specific FOXP3 mutation on Treg cell subsets. The findings suggest that the full-length FOXP3 isoform is important for maintaining Treg cell lineage stability but not essential for Treg cell activation.
CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Yanru Zhao, Xiaoyan Zheng, Miaojing Li, Jing Zhao, Xiaoning Wang, Huachao Zhu
Summary: Th17/Treg imbalance contributes to rejection in allo-HSCT. ADAR1 plays a critical role in regulating Foxp3 expression and improving Treg cell function by suppressing miR-21b production. In aGVHD mouse model, ADAR1 over-expression decreased Th17 proportion, increased Treg proportion, and improved tissue necrosis and reticular structure in liver and lung.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Immunology
Linlu Tian, Besim Ogretmen, Brian Y. Chung, Xue-Zhong Yu
Summary: Allogeneic hematopoietic cell transplantation is an effective immunotherapy against hematopoietic malignancies, but GVHD and tumor relapse are major concerns. Sphingolipid metabolism plays a crucial role in immune responses, highlighting the need to explore therapeutic strategies targeting sphingolipid metabolism.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Ning Wu, Ruoyang Liu, Shuang Liang, Haitao Gao, Lan-Ping Xu, Xiao-Hui Zhang, Jiangying Liu, Xiao-Jun Huang
Summary: In the development of aGVHD, gamma delta T cells were found to indirectly regulate the migration of CD4 T cells to target tissues, rather than directly triggering alloreactive responses. This study suggests a potential role for gamma delta T cells in recruiting alloreactive CD4 T cells through the expression of CXCR4, providing new insights into the mechanism of aGVHD and potential therapeutic targets.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Erika S. Varady, L. Angel Ayala, Pauline U. Nguyen, Vanessa M. Scarfone, Alborz Karimzadeh, Cuiwen Zhou, Xiyu Chen, Scott A. Greilach, Craig M. Walsh, Matthew A. Inlay
Summary: Donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation increases HSC engraftment and reduces the severity and incidence of graft-versus-host disease (GvHD) in allogeneic hosts.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Marisa K. Kilgour, Sarah MacPherson, Lauren G. Zacharias, Abigail E. Ellis, Ryan D. Sheldon, Elaine Y. Liu, Sarah Keyes, Brenna Pauly, Gillian Carleton, Bertrand Allard, Julian Smazynski, Kelsey S. Williams, Peter H. Watson, John Stagg, Brad H. Nelson, Ralph J. DeBerardinis, Russell G. Jones, Phineas T. Hamilton, Julian J. Lum
Summary: Immune regulatory metabolites in the tumor microenvironment, such as 1-methylnicotinamide (MNA), play a key role in modulating T cell responses. Despite the elevated levels of MNA in T cells infiltrating tumors, the enzyme catalyzing MNA transfer is restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete tumor-promoting cytokines, suggesting it as a potential immunotherapy target for human cancer treatment.
Article
Immunology
Thomas Krueger, Rebekka Wehner, Maik Herbig, Martin Kraeter, Michael Kramer, Jan Moritz Middeke, Friedrich Stoelzel, Catrin List, Katharina Egger-Heidrich, Raphael Teipel, Uta Oelschlaegel, Martin Wermke, Helena Jambor, Manja Wobus, Johannes Schetelig, Korinna Joehrens, Torsten Tonn, Julien Subburayalu, Marc Schmitz, Martin Bornhauser, Malte von Bonin
Summary: Functional impairment of the bone marrow niche, particularly a decrease in mesenchymal stromal cells (MSCs), is associated with cytopenia and graft failure after hematopoietic cell transplantation. Acute graft-versus-host disease (aGvHD) is shown to significantly reduce MSC numbers, and this reduction can be observed before clinical onset of aGvHD. The different phenotypic and functional characteristics of MSCs depending on the occurrence of aGvHD suggest that they may contribute to alloreactivity after transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Riccardo Masetti, Daniele Zama, Davide Leardini, Edoardo Muratore, Silvia Turroni, Patrizia Brigidi, Andrea Pession
Summary: The gut microbiome plays a significant role in hematopoietic stem cell transplantation, with its metabolites mediating interactions between intestinal microbial communities and the host. New data offer a fresh perspective on the role of microbiome-derived metabolites in transplant settings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Hyunju Oh, Jingyao Zhao, Yenkel Grinberg-Bleyer, Thomas S. Postler, Pingzhang Wang, Sung-Gyoo Park, Raul Rabadan, Matthew S. Hayden, Sankar Ghosh
Summary: This study demonstrates the essential role of PDK1 in both T cell activation and Treg cell suppressive activity, with PDK1 regulating Treg cell gene expression and suppressor function primarily through the NF-κB pathway.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Eshrak Al-Shaibani, Rhida Bautista, Jeffrey H. Lipton, Dennis D. Kim, Auro Viswabandya, Rajat Kumar, Wilson Lam, Arjun D. Law, Zeyad Al-Shaibani, Armin Gerbitz, Ivan Pasic, Jonas Mattsson, Fotios Michelis
Summary: Allogeneic hematopoietic cell transplantation is a potential cure for hematological diseases, but relapse and graft failure remain major causes of treatment failure. This study compared the outcomes of donor lymphocyte infusions (DLI) and second-HCT for patients with relapse or graft failure after the first transplantation. The results showed that second-HCT had better survival rates for relapse patients compared to DLI. Donor mismatch, Karnofsky Performance Status (KPS), and time from first-HCT to intervention were identified as independent prognostic factors for survival.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2022)
Article
Immunology
Maud D'Aveni, Anne-Beatrice Notarantonio, Viviane A. Agbogan, Allan Bertrand, Guillemette Fouquet, Pauline Gastineau, Meriem Garfa-Traore, Marcelo De Carvalho, Olivier Hermine, Marie-Therese Rubio, Flora Zavala
Summary: Allo-HSCT often uses G-CSF to mobilize PBSCs, which can enhance the immunosuppressant effect of Tregs on alloreactive T cells, reducing the lethality of GVHD in mice and potentially in humans. This suggests G-CSF-mobilized MPPs could be a valuable cellular therapy to expand donor Tregs and prevent GVHD in allo-HSCT for leukemia treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Alvaro Teijeira, Itziar Migueliz, Saray Garasa, Vaios Karanikas, Carlos Luri, Asunta Cirella, Irene Olivera, Marta Canamero, Maite Alvarez, Maria C. Ochoa, Ana Rouzaut, Maria E. Rodriguez-Ruiz, Miguel F. Sanmamed, Christian Klein, Pablo Umana, Mariano Ponz, Marina Bacac, Ignacio Melero
Summary: In this study, the performance of the CEA-CD3 T cell bispecific antibody cibisatamab in three-dimensional tumor organoids cocultured with T cells was investigated using time-lapse confocal microscopy. The results showed that the killing of tumor cells was dependent on the levels of surface CEA expression, and the higher affinity CEACAM5-CD3 bispecific antibody remained active on low CEA expressing organoids. Additionally, the coculture of tumor organoids, autologous fibroblasts, and T cells demonstrated a costimulatory effect of anti-FAP-4-1BBL antibody, leading to enhanced tumor cell killing.
Article
Oncology
Javier Glez-Vaz, Arantza Azpilikueta, Irene Olivera, Assunta Cirella, Alvaro Teijeira, Maria C. Ochoa, Maite Alvarez, Inaki Eguren-Santamaria, Carlos Luri-Rey, Maria E. Rodriguez-Ruiz, Xinxin Nie, Lieping Chen, Sonia Guedan, Miguel F. Sanamed, Jose Luis Perez Gracia, Ignacio Melero
Summary: CD137 agonists have shown efficacy in tumor treatment, and the levels of sCD137 and CD137 surface expression can serve as quantitative parameters for therapeutic activity.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Irene Olivera, Rebeca Sanz-Pamplona, Elixabet Bolanos, Inmaculada Rodriguez, Inaki Etxeberria, Assunta Cirella, Josune Egea, Saray Garasa, Itziar Migueliz, Inaki Eguren-Santamaria, Miguel F. Sanmamed, Javier Glez-Vaz, Arantza Azpilikueta, Maite Alvarez, Maria C. Ochoa, Beatrice Malacrida, David Propper, Carlos E. de Andrea, Pedro Berraondo, Frances R. Balkwill, Alvaro Teijeira, Ignacio Melero
Summary: In the tumor microenvironment, IL-8 correlates with poor response to checkpoint inhibitors and attracts immunosuppressive myeloid cells. TNF alpha and IL-1 beta are major inducers of IL-8 expression on malignant cells, which can be interfered with by clinically available neutralizing agents.
Article
Oncology
Angela Bella, Leire Arrizabalaga, Claudia Augusta Di Trani, Assunta Cirella, Myriam Fernandez-Sendin, Celia Gomar, Joan Salvador Russo-Cabrera, Inmaculada Rodriguez, Jose Gonzalez-Gomariz, Maite Alvarez, Alvaro Teijeira, Jose Medina-Echeverz, Maria Hinterberger, Hubertus Hochrein, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: This study evaluated different recombinant-modified vaccinia virus Ankara (rMVA) vectors in preclinical peritoneal carcinomatosis models and found that the vector encoding both CD40L and CD137L can enhance immune response and improve survival in mice with peritoneal carcinomatosis.
Review
Cell Biology
Alberto Mendoza-Valderrey, Maite Alvarez, Andrea De Maria, Kim Margolin, Ignacio Melero, Maria Libera Ascierto
Summary: NK cells, with their unique capacity to attack cancer cells without antigen specificity, are being explored as a powerful tool for immunotherapy against tumors. Various strategies are being pursued to maximize the anti-tumor properties of NK cells in the clinic, with the need for further optimization to enhance the clinical outcome of NK cell-based immunotherapy targeting tumors.
Meeting Abstract
Hematology
Antonio Pierini, Loredana Ruggeri, Simonetta Saldi, Sara Tricarico, Francesca Marzuttini, Valerio Viglione, Rebecca Sembenico, Tiziana Zei, Roberta Lacucci Ostini, Antonella Mancusi, Roberto Limongello, Olivia Minelli, Gianluca Ingrosso, Adelmo Terenzi, Maria Paola Martelli, Maurizio Caniglia, Cristina Mecucci, Andrea Velardi, Massimo Fabrizio Martelli, Cynthia Aristei, Alessandra Carotti
Article
Oncology
Claudia Augusta Di Trani, Assunta Cirella, Leire Arrizabalaga, Angela Bella, Myriam Fernandez-Sendin, Joan Salvador Russo-Cabrera, Celia Gomar, Irene Olivera, Elizabeth Bolanos, Jose Gonzalez-Gomariz, Maite Alvarez, Inaki Etxeberria, Belen Palencia, Alvaro Teijeira, Ignacio Melero, Pedro Berraondo, Fernando Aranda
Summary: Previous studies have found that local delivery of tumor antigen-specific CD8(+) T lymphocytes transiently expressing single-chain IL-12 mRNA is highly effective in treating tumors. In this study, intracavitary adoptive T cell therapy was used to treat peritoneal dissemination of B16-OVA and PANC02-OVA tumors, and it was found that intraperitoneal administration of T cells promoted homing to the omentum more effectively than intravenous administration. Transient IL-12 expression resulted in a favorable reprogramming of the tumor immune microenvironment and longer persistence of transferred T lymphocytes, leading to the development of immunity to endogenous antigens after primary tumor eradication.
Article
Oncology
Maria E. Rodriguez-Ruiz, Irantzu Serrano-Mendioroz, Eneko Garate-Soraluze, Paloma Sanchez-Mateos, Celia Barrio-Alonso, Inmaculada Rodriguez Lopez, Victor Diaz Pascual, Leire Arbea Moreno, Maite Alvarez, Miguel F. Sanmamed, Jose Luis Perez-Gracia, Helena Escuin-Ordinas, Marisol Quintero, Ignacio Melero
Summary: This study demonstrates that local BO-112 immunotherapy and focal irradiation can synergistically achieve local tumor control. Furthermore, irradiation plus BO-112 in one of the tumor lesions enhances the therapeutic effects on distant irradiated lesions that were not injected with BO-112.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Maite Alvarez, Carmen Molina, Saray Garasa, Maria C. Ochoa, Maria E. Rodriguez-Ruiz, Gabriel Gomis, Assunta Cirella, Irene Olivera, Javier Glez-Vaz, Jose Gonzalez-Gomariz, Carlos luri-Rey, Arantza Azpilikueta, Elixabet Bolanos, Alvaro Teijeira, Pedro Berraondo, Marisol Quintero, Ignacio Melero
Summary: The poly I:C-based viral mimetic BO-112 has been found to effectively reduce tumor metastasis when intratumorally delivered, particularly when combined with systemic anti-PD-1 mAbs. This neoadjuvant immunotherapy approach relies on antigen-specific effector CD8 T cells and cDC1 antigen-presenting cells.
Article
Cell Biology
Irene Olivera, Elixabet Bolanos, Jose Gonzalez-Gomariz, Sandra Hervas-Stubbs, Karina V. Marino, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Josune Egea, Javier Glez-Vaz, Saray Garasa, Maite Alvarez, Inaki Eguren-Santamaria, Sonia Guedan, Miguel F. Sanmamed, Pedro Berraondo, Gabriel A. Rabinovich, Alvaro Teijeira, Ignacio Melero
Summary: Engineering tumor-specific CD8 T cells with IL-12 mRNA enhances their therapeutic potency when delivered intratumorally.
CELL REPORTS MEDICINE
(2023)
Article
Cell Biology
Maria Carmen Ochoa, Sandra Sanchez-Gregorio, Carlos E. de Andrea, Saray Garasa, Maite Alvarez, Irene Olivera, Javier Glez-Vaz, Carlos Luri-Rey, Inaki Etxeberria, Assunta Cirella, Arantza Azpilikueta, Pedro Berraondo, Josepmaria Argemi, Bruno Sangro, Alvaro Teijeira, Ignacio Melero
Summary: Immune checkpoint-inhibitor combinations are the best therapeutic option for advanced hepatocellular carcinoma (HCC) patients, and the efficacy can be further improved by combining recombinant IL-2 or anti-CD137 mAb with anti-CTLA-4 + anti-PD1 mAbs treatment. A multifocal HCC model was developed to test immunotherapies, and the combination of tumor-specific adoptive T cell therapy with aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 regimens showed synergistic efficacy. The combined immunotherapy treatments enhanced T cell infiltration and the intratumoral performance of T lymphocytes.
CELL REPORTS MEDICINE
(2023)
Article
Medicine, Research & Experimental
Ignacio Melero, Maria C. Ochoa, Carmen Molina, Sandra Sanchez-Gregorio, Saray Garasa, Carlos Luri-Rey, Sandra Hervas-Stubbs, Noelia Casares, Edurne Elizalde, Gabriel Gomis, Assunta Cirella, Pedro Berraondo, Alvaro Teijeira, Maite Alvarez
Summary: NK cell reactivity against cancer is suppressed in the tumor microenvironment through the interaction of the inhibitory receptor NKG2A with non-classical MHC-I molecules. Injection of anti-NKG2A and anti-Qa-1(b) antibodies enhances the therapeutic effects of NK cells and shows partial efficacy against distant tumors. In experiments with human cancer cells expressing HLA-E, injection of activated allogeneic human NK cells and anti-NKG2A antibodies synergistically achieve therapeutic effects.
EMBO MOLECULAR MEDICINE
(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)
