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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

PD-1 blockage delays murine squamous cell carcinoma development

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Author(s):
Belai, Eduardo Bertoli [1] ; de Oliveira, Carine Ervolino [2] ; Gasparoto, Thas Helena [1] ; Ramos, Rodrigo Nalio [1] ; Torres, Sergio Aparecido [1] ; Garlet, Gustavo Pompermaier [1] ; Cavassani, Karen Angelica [3] ; Silva, Joao Santana [4] ; Campanelli, Ana Paula [1]
Total Authors: 9
Affiliation:
[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, BR-17012901 Sao Paulo - Brazil
[2] Univ Sao Paulo, Bauru Sch Dent, Dept Stomatol, BR-17012901 Sao Paulo - Brazil
[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 - USA
[4] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Carcinogenesis; v. 35, n. 2, p. 424-431, FEB 2014.
Web of Science Citations: 18
Abstract

Engagement of programmed death-1 (PD-1) with its two ligands {[}programmed death ligand-1 (PD-L1) and PD-L2] has been associated with the suppression of tumor-reactive T cells; however, the underlying mechanism for this T-cell dysfunction is not clear. We hypothesized that PD-1 and PD-L1 signals are, in part, responsible for squamous cell carcinoma (SCC) escape from immune antitumor regulation by modulation of the tumor environment. In the present study, we used a multistage model of SCC to examine the role of PD-1/PD-L1 activation during tumor development. Tumor sites presented an increased percentage of CD4 and CD8 T cells expressing PD-1 when compared with non-tumorigenic control mice, whereas the expression of PD-L1 was particularly increased in F4/80 macrophages in tumor sites. Further, the systemic immune neutralization of PD-1 resulted in a decreased number and delayed incidence rate of papillomas followed by a differential expression of cytokeratins, suggesting that the PD-1PD-L1 interaction contributes to the progression of SCC by downregulation of antitumor responses. In fact, blocking PD-1 increased the percentage of CD8 and CD4 T cells, and the levels of interferon- in the tumor sites. Our results indicated involvement of PD-1 T cells in SCC development and in the modulation of the inflammatory immune response. (AU)

FAPESP's process: 08/10999-7 - Modulation of immune response during squamous-cell carcinoma development and progression
Grantee:Ana Paula Campanelli
Support Opportunities: Regular Research Grants
FAPESP's process: 09/14127-7 - The role of inflammasomes in chemically induced tumor
Grantee:Thaís Helena Gasparoto
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 09/03471-9 - Modulation of immune response during squamous-cell carcinoma development and progression
Grantee:Eduardo Bertoli Belai
Support Opportunities: Scholarships in Brazil - Master