Dr. Ana Carolina Ramos Moreno is a FAPESP Young Investigator Fellow at the Department of Microbiology of the Institute of Biomedical Sciences of the University of São Paulo (2016 – current). She is graduated in Pharmacy and Biochemistry at the University of São Paulo (1996-2000), and holds a master’s degree (2001-2004) and a PhD (2004-2008) in Microbiology at the Graduate Program in Clinical Analyzes, Faculty of Pharmaceutical Sciences, University from São Paulo. She was a postdoctoral fellow in different areas of health, being Biochemistry of Tumors (melanomas and glioblastomas) at the Faculty of Pharmaceutical Sciences, University of São Paulo (2008-2013); Cancer Cell Biology, at the National Center for Oncological Research (CNIO), Madrid, Spain (2012); Microbiology, focusing on the development of therapeutic vaccines for HPV-associated tumors, at the Institute of Biomedical Sciences of the University of São Paulo (2014-2017). Currently, she is Researcher-Collaborator at the Department of Microbiology of the Institute of Biomedical Sciences of the University of São Paulo. Her research area is based on Microbiology, Immunology and Cell Biology, focusing on the study of pathogen-host cell interaction, bacterial pathogenicity, and immunotherapies for tumors associated with microorganisms.
In 2014, Dr. Moreno joined the Laboratory of Vaccine Development (LDV), led by Prof. Luís Carlos de Souza Ferreira and Prof. Rita de Cássia Café Ferreira, to start her own research group, focused on the use of immunometabolic adjuvants (melatonin and/or IDO1 inhibitors) as a new and promising alternative for improving the efficacy of immunotherapeutic treatments of HPV-associated tumors.
Indoleamine 2,3 dioxygenase in the biology of papillomaviruses-induced tumors: neoadjuvant effects on the immunotherapy of tumors
In the last twelve years, solid evidence showed that the enzyme Indoleamine 2,3 dioxygenase-1 (IDO) is an important mediator of immune tolerance. While the similarities between IDO regulatory mechanisms and the molecular signature associated with cervical cancer and other tumors induced by human papillomavirus (HPV), the active role of IDO in these tumors has not been studied. Here, we will study two important fields that can support the success of an antitumor therapeutic approach. In the first phase, we will evaluate the link of the molecular mechanisms related to IDO and the profile of the immune response regarding HPV-associated tumors. Therefore, we will evaluate the cellular and molecular parameters using different in vitro and in vivo experimental models, as well as human biopsies. Moreover, knockout mice IDO (-/-), aryl hydrocarbon receptor (AHR) Ahr (-/-) and IL-6 (-/-) will be used for a robust assessment of the role of IDO in this tumor model. Once the parameters were established, the second stage of our research aims to develop a therapeutic approach based on the consortium of an IDO inhibitor (1-methyl-tryptophan) and an anti-oxidant (melatonin) with a specific anti-tumor vaccine formulation against HPV-induced tumors. We will evaluate the phenotype and function of specific T CD8+ cells, and other cell parameters, to establish the relevance of these events in a protective immunity activation achieved by the combination of the neoadjuvant therapy and antitumor vaccines. This research has innovative features, which could impact on the translation of basic science into clinical interventions and promotes the nucleation of a new research frontline in the University of São Paulo.