KEY TAKEAWAYS
- The study aimed to examine HPV E6/E7, p53-specific T-cell responses, and immune checkpoint blockade in patients with HPV-positive HNSCC.
- The findings showed that checkpoint blockade enhances T-cell responses in HPV-positive HNSCC patients’ peripheral blood.
Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is clinically and immunologically distinct from HPV-negative HNSCC.
Kazuaki Chikamatsu and the team aimed to examine the presence of HPV E6/E7 and wild-type p53-specific T-cell responses and the impact of immune checkpoint blockade in patients with HPV-positive HNSCC.
Researchers stimulated peripheral blood mononuclear cells (PBMCs) from patients with HPV-positive HNSCC having HPV E6/E7 or wild-type p53-derived peptide mixtures. They evaluated the cells using an interferon-γ enzyme-linked immunosorbent spot assay and analyzed T-cell subsets and T cells expressing immune checkpoint molecules through flow cytometry.
The results revealed that HPV E6/E7-specific T cells were detected in 22 of 23 patients (95.7%), while wild-type p53-specific T cells were found in 3 of 20 patients (15.0%). Using whole proteins instead of peptides, wild-type p53-specific T-cell responses were observed in 7 of 16 patients (43.8%).
Immune checkpoint blockade enhanced wild-type p53-specific T-cell responses in 9 of 20 patients (45.0%). Flow cytometric analysis of PBMCs showed that responders with enhanced wild-type p53-specific T-cell responses following immune checkpoint blockade had significantly higher proportions of Ki-67+CD4+ T cells, Ki-67+CD8+ T cells, regulatory T cells, PD-1+CD4+ T cells, and TIM-3+CD4+ T cells compared to non-responders.
The study concluded that tumor antigen-specific T cells are present in the peripheral blood of patients with HPV-positive HNSCC. Checkpoint pathway blockade can enhance T-cell responses in certain patients, likely through activated T cells, regulatory T cells, and/or exhausted CD4+ T cells.
No funding information was available.
Source: https://pubmed.ncbi.nlm.nih.gov/38925841/
Chikamatsu K, Ida S, Masuda K, et al. (2024). “Enhancement of Tumor Antigen-specific T-cell Responses by Immune Checkpoint Blockade in Human Papillomavirus-related Head and Neck Squamous Cell Carcinoma.” Anticancer Res. 2024 Jul;44(7):2921-2931. doi: 10.21873/anticanres.17104. PMID: 38925841.
