Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Tumoral and Systemic Immune Correlates of Response to Concurrent Pembrolizumab and Chemoradiotherapy in Patients with Resected High-Risk Head and Neck Squamous Cell Carcinoma.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод пока не подготовлен
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Vujanovic Lazar, Torres-Saavedra Pedro, Tu Fei, Uppaluri Ravindra, Yao Min, Chen Josephine, Jordan Richard, Geiger Jessica L, Jujjavarapu Srinivas, Chakravarti Arnab, Phan Minh, Siddiqui Farzan, Kulkarni Aditi, Upadhyay Pragati, Isett Brian Robert, Sica Gabriel L, Reeder Carly, Bao Riyue, Chen Jie, Joy Marion, Freeman Tanner, Harris Jonathan, Le Quynh-Thu, Bauman Julie E, Ferris Robert L
Аннотация
PURPOSE: Patients with pathologically high-risk, human papillomavirus-negative squamous cell carcinoma of the head and neck (HNSCC) recur frequently despite adjuvant cisplatin radiotherapy (CRT). As CRT can upregulate PD-1/L1 immune checkpoints, adding pembrolizumab may reverse treatment-induced immunosuppression. NRG-HN003 was a phase I trial assessing the safety and recommended phase II schedule of adjuvant pembrolizumab with CRT. Here, we report exploratory immune and genomic correlates of disease-free survival (DFS).
PATIENTS AND METHODS: Thirty-four patients received pembrolizumab with CRT. PD-L1 expression was quantified by combined positive score (CPS), and spatial localization of PD-L1+ cells was assessed by multispectral imaging of baseline tumors. Disruptive TP53 mutations were evaluated by whole-exome sequencing. Soluble serum biomarkers were evaluated by Luminex, and circulating immune subsets were profiled by spectral flow cytometry at baseline and after treatment.
RESULTS: Patients with PD-L1 CPS ≥20 showed numerically lower DFS than those with CPS <20; however, higher densities of PD-L1+ stromal cells were associated with more favorable outcomes. Disruptive TP53 mutations were not a significant negative prognostic factor. Among soluble markers at baseline, elevated serum arginase-1 was associated with inferior DFS, whereas higher levels of GM-CSF, IL-5 and nectin-2 were associated with more favorable outcomes. In circulating immune cells, higher baseline frequencies of CD8+ granzyme K+ T cells, as well as higher posttreatment frequencies of CD8+ CD39+ and regulatory CD4+ T cells, were associated with improved DFS. Increased effector and central memory T cell populations, especially after treatment, also showed favorable associations with DFS.
CONCLUSIONS: These findings highlight multiple potential immunologic correlates of pembrolizumab with CRT in high-risk HNSCC, supporting further evaluation and validation in larger, adequately powered trials.
PATIENTS AND METHODS: Thirty-four patients received pembrolizumab with CRT. PD-L1 expression was quantified by combined positive score (CPS), and spatial localization of PD-L1+ cells was assessed by multispectral imaging of baseline tumors. Disruptive TP53 mutations were evaluated by whole-exome sequencing. Soluble serum biomarkers were evaluated by Luminex, and circulating immune subsets were profiled by spectral flow cytometry at baseline and after treatment.
RESULTS: Patients with PD-L1 CPS ≥20 showed numerically lower DFS than those with CPS <20; however, higher densities of PD-L1+ stromal cells were associated with more favorable outcomes. Disruptive TP53 mutations were not a significant negative prognostic factor. Among soluble markers at baseline, elevated serum arginase-1 was associated with inferior DFS, whereas higher levels of GM-CSF, IL-5 and nectin-2 were associated with more favorable outcomes. In circulating immune cells, higher baseline frequencies of CD8+ granzyme K+ T cells, as well as higher posttreatment frequencies of CD8+ CD39+ and regulatory CD4+ T cells, were associated with improved DFS. Increased effector and central memory T cell populations, especially after treatment, also showed favorable associations with DFS.
CONCLUSIONS: These findings highlight multiple potential immunologic correlates of pembrolizumab with CRT in high-risk HNSCC, supporting further evaluation and validation in larger, adequately powered trials.