Randomized trial finds that a composite immune checkpoint phenotype predicts treatment response in HNSCC, suggesting potential for improved patient outcomes.
Background Predictive biomarkers for response to PD‐1 blockade in recurrent or metastatic HNSCC remain limited. We investigated whether coordinated expression of multiple inhibitory immune checkpoints defines a clinically relevant biomarker phenotype. Methods Clinical and immunohistochemical data from 78 patients with recurrent or metastatic HNSCC treated with nivolumab or pembrolizumab were retrospectively analyzed. Expression of PD‐L1, LAG‐3, TIM‐3, and IDO1 on tumor‐infiltrating immune cells was assessed. A composite immune checkpoint phenotype was defined by concurrent immune‐cell expression of these markers. Associations with treatment response and survival were analyzed. Results The composite immune checkpoint phenotype was observed in 10.1% of tumors and was strongly associated with objective response ( p < 0.001), disease control ( p = 0.006), and improved overall, disease‐specific, and progression‐free survival (all p ≤ 0.030). In multivariable analysis, this phenotype independently predicted overall ( p = 0.031) and disease‐specific survival ( p = 0.011). Conclusion Coordinated expression of multiple inhibitory immune checkpoints identifies an inflamed tumor microenvironment associated with improved outcomes following PD‐1 blockade in HNSCC.
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Fiedler et al. (2026) studied this question.
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