Immunomethylomic profiles of long-term head and neck squamous cell carcinoma survivors on immune checkpoint inhibitors

<b>Aim:</b> This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. <b>Methods:</b> Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. <b>Results:</b> There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy. <b>Conclusion:</b> These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients. While immunotherapy has improved prognosis, the average percentage of head and neck squamous cell carcinoma (HNSCC) patients who respond to immunotherapy remains low at 15–20%. There are still significant gaps in understanding immunotherapy response, including a limited clinical ability to identify patients who would benefit from immune checkpoint inhibitors. This study revealed significant variations in the complete immune profile of these patients at different treatment stages, from the baseline to the 18th treatment cycle. There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immune checkpoint inhibitor therapy, which then returned to baseline levels after a year. compared with healthy individuals, HNSCC responders had significantly lower levels of CD4 T and B cells and higher levels of monocytes, both at baseline and throughout the year of immune checkpoint inhibitor treatment. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy.