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Tumor microenvironment, inflammation and immunomodulation: therapeutic possibilities and prognostic markers

Grant number: 14/19326-6
Support type:Regular Research Grants
Duration: August 01, 2015 - July 31, 2018
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Ana Paula Lepique
Grantee:Ana Paula Lepique
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Our laboratory has been investigating interactions between tumor and inflammatory cells, as well as systemic effects displayed by the tumor in its host. Our main focus has been Human papillomavirus (HPV) associated tumors. HPV infections are the main etiologic factor for the development of cervical cancer, as well as a percentage of other anogenital and oropharingeal cancers.We have recently shown that these tumors display effects on the host like leukocytosis, reduction of antigen presentation efficiency, reduction of NFºB activation in professional antigen presenting cells (APCs). While working in the tumor and inflammatory cells interactions to unravel the mechanisms behind these effects, we are also suggesting interfering in the above processes to inhibit tumor growth: neutralization of cytokines that may play a role in leukocytosis, activation of the NFºB pathway in APCs via treatment with CD40 agonist and test of their potential to activate antitumor responses in T cells. These studies are complementary to an ongoing study where we are characterizing the inflammatory infiltrate in cervical lesions of various grades. We have demonstrated that neutrophils infiltrate these lesions and, in cancer, their frequency is negatively correlated with CD8 T cells frequency. In this project, we intend to characterize the functional profile of these neutrophils and study their role in tumor progression. The results here obtained might be extrapolated to other HPV associated tumors or tumors with different etiologies. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
STONE, SIMONE CARDOZO; MARQUES ROSSETTI, RENATA ARIZA; FERNANDEZ ALVAREZ, KARLA LUCIA; CARVALHO, JESUS PAULA; RAMOS MARGARIDO, PAULO FRANCISCO; BARACAT, EDMUND CHADA; TACLA, MARICY; BOCCARDO, ENRIQUE; YOKOCHI, KAORI; LORENZI, NOELY PAULA; et al. Lactate secreted by cervical cancer cells modulates macrophage phenotype. Journal of Leukocyte Biology, v. 105, n. 5, p. 1041-1054, . (14/19326-6, 08/57889-1)
FERNANDEZ ALVAREZ, KARLA LUCIA; BELDI, MARIANA; SARMANHO, FABIANE; MARQUES ROSSETTI, RENATA ARIZA; FARINA SILVEIRA, CAIO RAONY; MOTA, GIANA RABELLO; ANDREOLI, MARIA ANTONIETA; DE CARVALHO CARUSO, ELIANA DIAS; KAMILLOS, MARCIA FERREIRA; SOUZA, ANA MARTA; et al. Local and systemic immunomodulatory mechanisms triggered by Human Papillomavirus transformed cells: a potential role for G-CSF and neutrophils. SCIENTIFIC REPORTS, v. 7, . (14/19326-6, 08/57889-1)
FARINA SILVEIRA, CAIO RAONY; CIPELLI, MARCELLA; MANZINE, CAROLINA; RABELO-SANTOS, SILVIA HELENA; ZEFERINO, LUIZ CARLOS; RODRIGUEZ, GRETEL RODRIGUEZ; DE ASSIS, JOSIANE BETIM; HEBSTER, SUELLEN; BERNADINELLI, ISABEL; LAGINHA, FABIO; et al. Swainsonine, an alpha-mannosidase inhibitor, may worsen cervical cancer progression through the increase in myeloid derived suppressor cells population. PLoS One, v. 14, n. 3, . (14/19326-6, 08/57889-1)
MARQUES ROSSETTI, RENATA ARIZA; CRISTINA LORENZI, NOELY PAULA; YOKOCHI, KAORI; SARTOR DE FARIA ROSA, MARIA BEATRIZ; BENEVIDES, LUCIANA; RAMOS MARGARIDO, PAULO FRANCISCO; BARACAT, EDMUND CHADA; CARVALHO, JESUS PAULA; VILLA, LUISA LINA; LEPIQUE, ANA PAULA. B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses. PLoS One, v. 13, n. 7, . (11/11121-8, 14/19326-6, 10/20010-2)
ROSSETTI, RENATA A. M.; DA SILVA-JUNIOR, ILDEFONSO A.; R RODRIGUEZ, GRETEL; ALVAREZ, KARLA L. F.; STONE, SIMONE C.; CIPELLI, MARCELLA; SILVEIRA, CAIO R. F.; BELDI, MARIANA CARMEZIM; MOTA, GIANA R.; MARGARIDO, PAULO F. R.; et al. Local and Systemic STAT3 and p65 NF-KappaB Expression as Progression Markers and Functional Targets for Patients With Cervical Cancer. FRONTIERS IN ONCOLOGY, v. 10, . (14/19326-6, 13/26856-9, 16/16149-1, 18/16989-5, 11/20499-4)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.