Inflammatory signature and restriction of adaptive immunity are associated with unfavorable outcomes on immune checkpoint blockade in patients with advanced head and neck squamous cell carcinoma
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Background
In most patients with relapsed or metastatic head and neck squamous cell carcinoma (rmHNSCC), immunotherapy with PD-1 targeting antibodies does not yield durable responses. PD-L1 tissue expression - the most commonly assessed marker for checkpoint inhibiting antibodies - is an insufficient predictor of treatment outcome.
Methods
We evaluated various blood and tissue-based biomarkers in the context of immune checkpoint blockade-based treatment to find suitable response biomarkers in a clinical trial cohort of patients with rmHNSCC.
Results
The PD-L1 expression level in tumor or tumor microenvironment was not associated with treatment benefit. In contrast, inflammation-related markers such as IL-6, high peripheral neutrophils and high levels of cell-free DNA, as well as markers related to adaptive immune dysfunction such as altered T cell dynamics and secretion of immune checkpoint molecules, were associated with poor clinical outcomes. Patients lacking these high-risk markers performed remarkably well on inhibition of immune checkpoints with pembrolizumab.
Conclusions
Biomarker-guided patient selection for pembrolizumab monotherapy or novel combinatorial approaches - potentially including anti-inflammatory agents – for patients with immune-impaired, inflammatory profiles may be the next step in personalizing immunotherapy for these hard-to-treat patients.
