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RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Expression profile and in vitro blockade of programmed death-1 in human papillomavirus-negative head and neck
Ian-James Malm1,2, Tullia C Bruno2, Juan Fu1
1Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Background:
Treatment with a blocking programmed death-1 (αPD-1) antibody recently showed clinical efficacy for various tumor types. In this study, we characterized the expression profile of PD-1/programmed death-ligand-1 (PD-L1) and the potential of PD-1 blockade in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC).
Methods:
Lymphocytes from peripheral blood, draining lymph nodes, and the tumor were phenotyped for PD-1 expression, and their proliferative activity was assessed in the presence of blocking αPD-1 treatment. Primary tumor expression of PD-L1 was also analyzed using immunohistochemistry (IHC).
Results:
Lymphocyte PD-1 expression was abundant with highest expression in the tumor, and in vitro mixed lymphocyte reaction demonstrated that PD-1 blockade could induce T cell proliferation. Furthermore, tumor cells were found to have 3 distinct patterns of PD-L1 expression with over 78% of the specimens demonstrating strong PD-L1 positivity.
Conclusion:
Our data strongly supports the use of αPD-1 blockade in patients with HPV-negative HNSCC that are refractory to standard treatments.
Insights
Programmed death-1 (PD-1) blockade shows promise for HPV-negative head and neck squamous cell carcinoma (HNSCC). Blocking PD-1 can stimulate T cell proliferation, supporting its use in refractory HNSCC cases.
Area of Science:
- Immunology
- Oncology
- Head and Neck Cancer Research
Background:
- Programmed death-1 (PD-1) antibody therapy demonstrates clinical efficacy across diverse tumor types.
- This study investigates PD-1/programmed death-ligand-1 (PD-L1) expression and PD-1 blockade potential in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To characterize the expression profile of PD-1/PD-L1 in HPV-negative HNSCC.
- To evaluate the therapeutic potential of PD-1 blockade in this specific cancer type.
Main Methods:
- Phenotyping of lymphocytes (peripheral blood, lymph nodes, tumor) for PD-1 expression.
- Assessment of T cell proliferation under blocking PD-1 antibody treatment.
- Immunohistochemistry (IHC) analysis of PD-L1 expression in primary tumors.
Main Results:
- Abundant PD-1 expression observed on lymphocytes, particularly within the tumor microenvironment.
- In vitro studies confirmed that PD-1 blockade effectively induces T cell proliferation.
- Over 78% of HNSCC specimens exhibited strong PD-L1 positivity across three distinct expression patterns.
Conclusions:
- The findings provide strong evidence supporting the use of PD-1 blockade therapy.
- This approach is recommended for patients with HPV-negative HNSCC who are refractory to conventional treatments.
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