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Immune response modulation by tumor cells

Grant number: 10/20010-2
Support Opportunities:Regular Research Grants
Duration: April 01, 2011 - September 30, 2013
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Ana Paula Lepique
Grantee:Ana Paula Lepique
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Tumors are composed by complex microenvironment where different cell types are present. For instance, tumor cells, endothelial cells, inflammatory infiltrate, fibroblasts, and acellular elements as extracellular matrix and soluble molecules like cytokines. This setting is essential for tumor fate determination.Human Papillomavirus (HPV) associated tumors are a health problem in developing countries. In spite of the prophylactic vaccines, studies on the tolerance and viral immune evasion mechanisms are still very important, manly to support new therapeutic approaches towards the tumors.Using a HPV16 associated tumor model in mice, we are studying the cellular immune responses to viral antigens expressed by the tumor cells. We have shown that tumor infiltrating macrophages suppress anti-tumor T cells responses in a mechanism dependent on IL-10 expression (Lepique et al, 2009; Bolpetti et al, 2010). New data from our laboratory indicate that the tumor conditions the secondary lymphoid organs of the host inducing, for example, proliferation of myeloid cells in the spleen. Furthermore, cytokines expressed by the different tumor populations may also have systemic effects (Bolpetti et al, in preparation). Using a different experimental approach, we observed that adoptive transfer of lymphocytes with anti-CD40 to RAG-/- mice inhibits tumor growth in the recipient, which T cells only are not able to do. This project has a goal the study of signaling pathways activated in the immune system different populations in mice with HPV associated tumors. We also intend to study the role of CD40 in tumor growth. (AU)

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Scientific publications
(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)
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)
STONE, SIMONE CARDOZO; MARQUES ROSSETTI, RENATA ARIZA; BOLPETTI, ALINE; BOCCARDO, ENRIQUE; DE ARAUJO SOUZA, PATRICIA SAVIO; LEPIQUE, ANA PAULA. HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells. Journal of Leukocyte Biology, v. 96, n. 4, p. 619-631, . (08/03232-1, 10/20010-2)

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