Francesco Andreata
@San Raffaele University
San Raffaele University
San Raffaele University
EDUCATION
PhD in Immunology, Bio Sorbonne Paris Cité Doctoral School, Paris (France).
European Master in Genetics, University of Paris-Diderot and Milan-Bicocca in joint supervision.
Master in Biotechnologies, University of Milan-Bicocca (Milan), Italy.
Bachelor in Biotechnologies, University of Milan-Bicocca (Milan), Italy
RESEARCH INTERESTS
Immunology
Scopus Publications
Scopus Publications
Marta Sevieri, Francesco Andreata, Francesco Mainini, Lorena Signati, Francesca Piccotti, Marta Truffi, Arianna Bonizzi, Leopoldo Sitia, Claudia Pigliacelli, Carlo Morasso,et al.
Springer Science and Business Media LLC
AbstractDespite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity.Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing adverse effects, highlighting the pivotal role played by FerOX in mitigating DOX-induced toxicity towards T-cells, thereby positioning it as a promising DOX formulation. This study contributes valuable insights to modern cancer therapy and immunomodulation.
Francesco Andreata, Kelly D. Moynihan, Valeria Fumagalli, Pietro Di Lucia, Danielle C. Pappas, Keigo Kawashima, Irene Ni, Paul H. Bessette, Chiara Perucchini, Elisa Bono,et al.
American Association for the Advancement of Science (AAAS)
CD8 + T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8 + T cell dysfunction showed that interleukin-2 (IL-2)–based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2’s effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (T reg ) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively. To address this, we developed a cis-targeted CD8-IL2 fusion protein, aiming to selectively stimulate dysfunctional CD8 + T cells in chronic HBV. In a mouse model, CD8-IL2 boosted the number of HBV-reactive CD8 + T cells in the liver without substantially altering T reg or NK cell counts. These expanded CD8 + T cells exhibited increased interferon-γ and granzyme B production, demonstrating enhanced functionality. CD8-IL2 treatment resulted in substantial antiviral effects, evidenced by marked reductions in viremia and antigenemia and HBV core antigen–positive hepatocytes. In contrast, an untargeted CTRL-IL2 led to predominant NK cell expansion, minimal CD8 + T cell expansion, negligible changes in effector molecules, and minimal antiviral activity. Human CD8-IL2 trials in cynomolgus monkeys mirrored these results, achieving a roughly 20-fold increase in peripheral blood CD8 + T cells without affecting NK or T reg cell numbers. These data support the development of CD8-IL2 as a therapy for chronic HBV infection.
Francesco Andreata, Marc Clément, Robert A Benson, Juliette Hadchouel, Emanuele Procopio, Guillaume Even, Julie Vorbe, Samira Benadda, Véronique Ollivier, Benoit Ho-Tin-Noe,et al.
eLife Sciences Publications, Ltd
Effective neutrophil migration to sites of inflammation is crucial for host immunity. A coordinated cascade of steps allows intravascular leukocytes to counteract the shear stress, transmigrate through the endothelial layer, and move toward the extravascular, static environment. Those events are tightly orchestrated by integrins, but, while the molecular mechanisms leading to their activation have been characterized, the regulatory pathways promoting their detachment remain elusive. In light of this, it has long been known that platelet-endothelial cell adhesion molecule (Pecam1, also known as CD31) deficiency blocks leukocyte transmigration at the level of the outer vessel wall, yet the associated cellular defects are controversial. In this study, we combined an unbiased proteomic study with in vitro and in vivo single-cell tracking in mice to study the dynamics and role of CD31 during neutrophil migration. We found that CD31 localizes to the uropod of migrating neutrophils along with closed β2-integrin and is required for essential neutrophil actin/integrin polarization. Accordingly, the uropod of Pecam1-/- neutrophils is unable to detach from the extracellular matrix, while antagonizing integrin binding to extracellular matrix components rescues this in vivo migratory defect. Conversely, we showed that sustaining CD31 co-signaling actively favors uropod detachment and effective migration of extravasated neutrophils to sites of inflammation in vivo. Altogether, our results suggest that CD31 acts as a molecular rheostat controlling integrin-mediated adhesion at the uropod of egressed neutrophils, thereby triggering their detachment from the outer vessel wall to reach the inflammatory sites.
Matteo Iannacone, Francesco Andreata, and Luca G Guidotti
Elsevier BV
Matteo Iannacone, Camille Blériot, Francesco Andreata, Xenia Ficht, Chiara Laura, Jose M. Garcia-Manteiga, Stefan Uderhardt, and Florent Ginhoux
Elsevier BV
Valeria Fumagalli, Valentina Venzin, Pietro Di Lucia, Federica Moalli, Xenia Ficht, Gioia Ambrosi, Leonardo Giustini, Francesco Andreata, Marta Grillo, Diletta Magini,et al.
American Association for the Advancement of Science (AAAS)
Group 1 innate lymphoid cells (ILCs), which comprise both natural killer (NK) cells and ILC1s, are important innate effectors that can also positively and negatively influence adaptive immune responses. The latter function is generally ascribed to the ability of NK cells to recognize and kill activated T cells. Here, we used multiphoton intravital microscopy in mouse models of hepatitis B to study the intrahepatic behavior of group 1 ILCs and their cross-talk with hepatitis B virus (HBV)–specific CD8 + T cells. We found that hepatocellular antigen recognition by effector CD8 + T cells triggered a prominent increase in the number of hepatic NK cells and ILC1s. Group 1 ILCs colocalized and engaged in prolonged interactions with effector CD8 + T cells undergoing hepatocellular antigen recognition; however, they did not induce T cell apoptosis. Rather, group 1 ILCs constrained CD8 + T cell proliferation by controlling local interleukin-2 (IL-2) availability. Accordingly, group 1 ILC depletion, or genetic removal of their IL-2 receptor a chain, considerably increased the number of intrahepatic HBV-specific effector CD8 + T cells and the attendant immunopathology. Together, these results reveal a role for group 1 ILCs in controlling T cell–mediated liver immunopathology by limiting local IL-2 concentration and have implications for the treatment of chronic HBV infection.
Francesco Andreata, Camille Blériot, Pietro Di Lucia, Giorgia De Simone, Valeria Fumagalli, Xenia Ficht, Cristian Gabriel Beccaria, Mirela Kuka, Florent Ginhoux, and Matteo Iannacone
Elsevier BV
Andrea Cossarizza, Hyun‐Dong Chang, Andreas Radbruch, Sergio Abrignani, Richard Addo, Mübeccel Akdis, Immanuel Andrä, Francesco Andreata, Francesco Annunziato, Eduardo Arranz,et al.
Wiley
The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.
Camille Blériot, Emelie Barreby, Garett Dunsmore, Raphaelle Ballaire, Svetoslav Chakarov, Xenia Ficht, Giorgia De Simone, Francesco Andreata, Valeria Fumagalli, Wei Guo,et al.
Elsevier BV
Giorgia De Simone, Francesco Andreata, Camille Bleriot, Valeria Fumagalli, Chiara Laura, José M. Garcia-Manteiga, Pietro Di Lucia, Stefano Gilotto, Xenia Ficht, Federico F. De Ponti,et al.
Elsevier BV
F. Andreata, A. Bonizzi, M. Sevieri, M. Truffi, M. Monieri, L. Sitia, F. Silva, L. Sorrentino, R. Allevi, P. Zerbi,et al.
Springer Science and Business Media LLC
AbstractNeoadjuvant chemotherapy has been established as the standard of care for HER2-positive breast cancer since it allows cancer down-staging, up to pathological complete response. The standard of care in the neoadjuvant setting for HER2-positive breast cancer is a combination of highly cytotoxic drugs such as anthracyclines and the anti-HER2 monoclonal antibody. Despite this cocktail allows a pathological complete response in up to 50%, their co-administration is strongly limited by intrinsic cardiotoxicity. Therefore, only a sequential administration of anthracyclines and the anti-HER2 treatment is allowed. Here, we propose the anthracycline formulation in H-Ferritin nanocages as promising candidate to solve this unmet clinical need, thanks to its capability to increase anthracyclines efficacy while reducing their cardiotoxicity. Treating a murine model of HER2-positive breast cancer with co-administration of Trastuzumab and H-Ferritin anthracycline nanoformulation, we demonstrate an improved tumor penetration of drugs, leading to increased anticancer efficacy and reduced of cardiotoxicity.
Lucia Salvioni, Stefania Zuppone, Francesco Andreata, Matteo Monieri, Serena Mazzucchelli, Caterina Di Carlo, Lucia Morelli, Chiara Cordiglieri, Lorena Donnici, Raffaele De Francesco,et al.
Wiley
Jonathan Vigne, Sylvie Bay, Rachida Aid-Launais, Guillaume Pariscoat, Guillaume Rucher, Jean Sénémaud, Ariane Truffier, Nadège Anizan, Guillaume Even, Christelle Ganneau,et al.
Springer Science and Business Media LLC
AbstractThere is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before99mTc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [18F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of99mTc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of99mTc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellentin vitroandin vivostability were observed. SPECT/CT imaging showed a significant higher99mTc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [18F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between99mTc-HYNIC-D-P8RI uptake and inflammatory cell infiltration.99mTc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specificin vivoimaging of inflammatory processes.
Alexandre P. Bénéchet, Giorgia De Simone, Pietro Di Lucia, Francesco Cilenti, Giulia Barbiera, Nina Le Bert, Valeria Fumagalli, Eleonora Lusito, Federica Moalli, Valentina Bianchessi,et al.
Springer Science and Business Media LLC
Quoc Thang Hoang, Alexandre Nuzzo, Liliane Louedec, Sandrine Delbosc, Francesco Andreata, Jamila Khallou-Laschet, Maksud Assadi, Philippe Montravers, Dan Longrois, Olivier Corcos,et al.
Springer Science and Business Media LLC
Francesco Andreata, Varouna Syvannarath, Marc Clement, Sandrine Delbosc, Kevin Guedj, Giulia Fornasa, Jamila Khallou-Laschet, Marion Morvan, Guillaume Even, Emanuele Procopio,et al.
Elsevier BV
Petra El Khoury, Ronan Roussel, Frederic Fumeron, Yara Abou-Khalil, Gilberto Velho, Kamel Mohammedi, Marie-Paule Jacob, Philippe Gabriel Steg, Louis Potier, Youmna Ghaleb,et al.
Wiley
To investigate whether plasma concentrations of proprotein‐convertase‐subtilisin/kexin type 9 (PCSK9) were associated with cardiovascular (CV) events in two cohorts of patients with type 2 diabetes mellitus.
A. Sannier, N. Stroumza, G. Caligiuri, M. Le Borgne-Moynier, F. Andreata, J. Senemaud, L. Louedec, G. Even, A. T. Gaston, C. Deschildre,et al.
Wiley
Thymic function decreases progressively with age but may be boosted in certain circumstances. We questioned whether heart transplantation was such a situation and whether thymic function was related to the onset of rejection. Twenty‐eight antithymocyte globulin–treated heart transplant recipients were included. Patients diagnosed for an antibody‐mediated rejection on endomyocardial biopsy had a higher proportion of circulating recent thymic emigrant CD4+ T cells and T cell receptor excision circle levels than other transplanted subjects. Thymus volume and density, assessed by computed tomography in a subset of patients, was also higher in patients experiencing antibody‐mediated rejection. We demonstrate that thymic function is a major determinant of onset of antibody‐mediated rejection and question whether thymectomy could be a prophylactic strategy to prevent alloimmune humoral responses.
Chien-Chia Chen, Eric Pouliquen, Alexis Broisat, Francesco Andreata, Maud Racapé, Patrick Bruneval, Laurence Kessler, Mitra Ahmadi, Sandrine Bacot, Carole Saison-Delaplace,et al.
American Society for Clinical Investigation
Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies.
Marc Clement, Kevin Guedj, Francesco Andreata, Marion Morvan, Laetitia Bey, Jamila Khallou-Laschet, Anh-Thu Gaston, Sandrine Delbosc, Jean-Marc Alsac, Patrick Bruneval,et al.
Ovid Technologies (Wolters Kluwer Health)
Background— The atheromodulating activity of B cells during the development of atherosclerosis is well documented, but the mechanisms by which these cells are regulated have not been investigated. Methods and Results— Here, we analyzed the contribution of Qa-1–restricted CD8 + regulatory T cells to the control of the T follicular helper–germinal center B-cell axis during atherogenesis. Genetic disruption of CD8 + regulatory T cell function in atherosclerosis-prone apolipoprotein E knockout mice resulted in overactivation of this axis in secondary lymphoid organs, led to the increased development of tertiary lymphoid organs in the aorta, and enhanced disease development. In contrast, restoring control of the T follicular helper–germinal center B-cell axis by blocking the ICOS-ICOSL pathway reduced the development of atherosclerosis and the formation of tertiary lymphoid organs. Moreover, analyses of human atherosclerotic aneurysmal arteries by flow cytometry, gene expression analysis, and immunofluorescence confirmed the presence of T follicular helper cells within tertiary lymphoid organs. Conclusions— This study is the first to demonstrate that the T follicular helper–germinal center B-cell axis is proatherogenic and that CD8 + regulatory T cells control the germinal center reaction in both secondary and tertiary lymphoid organs. Therefore, disrupting this axis represents an innovative therapeutic approach.
Marc Clement, Giulia Fornasa, Stéphane Loyau, Marion Morvan, Francesco Andreata, Kevin Guedj, Jamila Khallou-Laschet, Paola Larghi, Delphine Le Roux, Georges Bismuth,et al.
Elsevier BV
Kevin Guedj, Jamila Khallou-Laschet, Marc Clement, Marion Morvan, Sandrine Delbosc, Anh-Thu Gaston, Francesco Andreata, Yves Castier, Catherine Deschildre, Jean-Baptiste Michel,et al.
Public Library of Science (PLoS)
Background Experimental atherosclerosis is characterized by the formation of tertiary lymphoid structures (TLOs) within the adventitial layer, which involves the chemokine-expressing aortic smooth muscle cells (SMCs). TLOs have also been described around human atherothrombotic arteries but the mechanisms of their formation remain poorly investigated. Herein, we tested whether human vascular SMCs play the role of chemokine-expressing cells that would trigger the formation of TLOs in atherothrombotic arteries. Results We first characterized, by flow cytometry and immunofluorescence analysis, the prevalence and cell composition of TLOs in human abdominal aneurysms of the aorta (AAAs), an evolutive form of atherothrombosis. Chemotaxis experiments revealed that the conditioned medium from AAA tissues recruited significantly more B and T lymphocytes than the conditioned medium from control (N-AAA) tissues. This was associated with an increase in the concentration of CXCL13, CXCL16, CCL19, CCL20, and CCL21 chemokines in the conditioned medium from AAA tissues. Immunofluorescence analysis of AAA cryosections revealed that α-SMA-positive SMCs were the main contributors to the chemokine production. These results were confirmed by RT-qPCR assays where we found that primary vascular SMCs from AAA tissues expressed significantly more chemokines than SMCs from N-AAA. Finally, in vitro experiments demonstrated that the inflammatory cytokines found to be increased in the conditioned medium from AAA were able to trigger the production of chemokines by primary SMCs. Conclusion Together, these results suggest that human vascular SMCs in atherothrombotic arteries, in response to inflammatory signals, are converted into chemokine-expressing cells that trigger the recruitment of immune cells and the formation of aortic TLOs.
Serena Mazzucchelli, Miriam Colombo, Paolo Verderio, Ewa Rozek, Francesco Andreata, Elisabetta Galbiati, Paolo Tortora, Fabio Corsi, and Davide Prosperi
Wiley
A generally underestimated concern isthe molecular organization at the nanoscale, which isa relevant consideration for protein ligands and is evencrucial when short peptides are used. To optimize therecognition by a specific biological receptor, the immobilizedpeptide needs to be stably ligated to the nanoparticle butsufficiently mobile to interact with the receptor. Indeed,peptides tend to bind to the surface of an MNP throughhydrophobic residues, which is promoted by entropic stabi-lization and electrostatic interactions and exploits polar anddissociated groups in the peptide sequence .