Blockade of CTLA-4 promotes the development of effector CD8(+) T lymphocytes and the therapeutic effect of vaccination with an attenuated protozoan expressing NY-ESO-1
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2015-03-01
Autores
Santos, Luara Isabela dos
Galvao-Filho, Bruno
Faria, Paula Cristina de
Junqueira, Caroline
Dutra, Miriam Santos
Ribeiro Teixeira, Santuza Maria
Rodrigues, Mauricio Martins [UNIFESP]
Ritter, Gerd
Bannard, Oliver
Fearon, Douglas Thomas
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The development of cancer immunotherapy has long been a challenge. Here, we report that prophylactic vaccination with a highly attenuated Trypanosoma cruzi strain expressing NY-ESO-1 (CL-14-NY-ESO-1) induces both effector memory and effector CD8(+) T lymphocytes that efficiently prevent tumor development. However, the therapeutic effect of such a vaccine is limited. We also demonstrate that blockade of Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) during vaccination enhances the frequency of NY-ESO-1-specific effector CD8(+) T cells producing IFN-gamma and promotes lymphocyte migration to the tumor infiltrate. As a result, therapy with CL-14-NY-ESO-1 together with anti-CTLA-4 is highly effective in controlling the development of an established melanoma.
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Cancer Immunology Immunotherapy. New York: Springer, v. 64, n. 3, p. 311-323, 2015.