Enhancement of Tumor Antigen-specific T-cell Responses by Immune Checkpoint Blockade in Human Papillomavirus-related Head and Neck Squamous Cell Carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.Tumor antigen-specific T cells are present in HPV-positive head and neck cancers. Immune checkpoint blockade can boost these T-cell responses in some patients, offering potential therapeutic avenues.
Area Of Science
- Immunology
- Oncology
- Virology
Background
- Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) exhibits distinct clinical and immunological characteristics compared to HPV-negative HNSCC.
- Investigating T-cell responses to tumor antigens HPV E6/E7 and wild-type p53 is crucial for understanding HPV-positive HNSCC immunity.
Purpose Of The Study
- To determine the presence of T-cell responses against HPV E6/E7 and wild-type p53 tumor antigens in patients with HPV-positive HNSCC.
- To evaluate the impact of immune checkpoint blockade on these T-cell responses.
Main Methods
- Peripheral blood mononuclear cells (PBMCs) were stimulated with HPV E6/E7 or wild-type p53 peptides.
- Interferon-γ enzyme-linked immunosorbent spot assay and flow cytometry were used to assess T-cell responses and immune checkpoint molecule expression.
Main Results
- High prevalence of HPV E6/E7-specific T cells (95.7%) and lower prevalence of wild-type p53-specific T cells (15.0%) were detected.
- Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 45.0% of patients.
- Responders showed increased proportions of activated T cells (Ki-67+), regulatory T cells (Tregs), and exhausted T cells (PD-1+, TIM-3+).
Conclusions
- Tumor antigen-specific T cells are detectable in the peripheral blood of patients with HPV-positive HNSCC.
- Immune checkpoint blockade can augment T-cell responses in a subset of these patients.
- Enhanced responses may involve activated T cells, Tregs, and/or exhausted CD4+ T cells.
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