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- Title
PD-1 blockage delays murine squamous cell carcinoma development.
- Authors
Belai, Eduardo Bertoli; de Oliveira, Carine Ervolino; Gasparoto, Thaís Helena; Ramos, Rodrigo Nalio; Torres, Sergio Aparecido; Garlet, Gustavo Pompermaier; Cavassani, Karen Angélica; Silva, João Santana; Campanelli, Ana Paula
- Abstract
Our results showed that the immune neutralization of PD-1+ cells resulted in decreased papilloma incidence associated with CD4+ and CD8+ T cells infiltrate, higher levels of interferon-γ and decreased levels of transforming growth factor-β in the tumor lesions. These findings support the role of PD-1 blockade as a promising component of immunotherapy against SCC.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-1–PD-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-γ 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.
- Subjects
PROGRAMMED cell death 1 receptors; SQUAMOUS cell carcinoma; PAPILLOMA; DISEASE incidence; CD antigens; T cells; INTERFERONS
- Publication
Carcinogenesis, 2014, Vol 35, Issue 2, p424
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgt305