Related Experiment Video
Updated: May 7, 2026
Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
PD-1 blockage delays murine squamous cell carcinoma development
Eduardo Bertoli Belai1, Carine Ervolino de Oliveira, Thaís Helena Gasparoto
1Department of Biological Sciences and.
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-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.
Insights
Programmed death-1 (PD-1) interaction with its ligands suppresses anti-tumor T cells in squamous cell carcinoma (SCC). Blocking PD-1 reduces tumor incidence and enhances anti-tumor immune responses in SCC.
Area of Science:
- Immunology
- Oncology
- Dermatology
Background:
- Programmed death-1 (PD-1) engagement with its ligands (PD-L1, PD-L2) inhibits tumor-reactive T cells, but the mechanism remains unclear.
- PD-1/PD-L1 signaling is implicated in immune evasion by various cancers, including squamous cell carcinoma (SCC).
Purpose of the Study:
- To investigate the role of PD-1/PD-L1 signaling in the immune evasion mechanisms of SCC.
- To determine if PD-1/PD-L1 interactions contribute to SCC progression by modulating the tumor microenvironment.
Main Methods:
- Utilized a multistage mouse model of SCC.
- Analyzed T cell populations (CD4+, CD8+) and PD-1 expression in tumor sites.
- Assessed PD-L1 expression on macrophages (F4/80+).
- Administered systemic immune neutralization of PD-1 and evaluated tumor development and immune markers.
Main Results:
- Tumor sites showed increased PD-1 expression on CD4+ and CD8+ T cells compared to controls.
- PD-L1 expression was notably elevated on macrophages within tumor sites.
- Blocking PD-1 led to reduced papilloma incidence and delayed tumor development.
- PD-1 blockade increased CD8+, CD4+ T cell percentages and interferon-gamma levels at tumor sites.
Conclusions:
- PD-1(+) T cells are involved in SCC development.
- The PD-1/PD-L1 pathway contributes to SCC progression by downregulating anti-tumor immune responses.
- Modulating the PD-1/PD-L1 interaction can enhance anti-tumor immunity in SCC.
