Abstract
BackgroundImmunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Therefore, the aim of this study was to identify predictive biomarkers of immunotherapy response for HNSCC in order to improve treatment outcomes.MethodsSurvival analyses and comparative efficacy evaluation were performed to investigate prognostic and therapeutic impact factors in patients with advanced HNSCC following immunotherapy, and to examine the effects of factors including gene mutations, tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and immune cell infiltration on the survival and efficacy.ResultsAnti-PD-1 treatment led to a prolonged overall survival (OS) in HNSCC patients with gene mutations compared with those without the mutations, while no significant difference in the OS was found between the two groups of patients. And no marked association between the MATH value and OS was detected in HNSCC patients, whereas patients with either high TMB scores in tissues and blood or high immune cell infiltration displayed a significantly longer OS. Further analysis with efficacy as the primary endpoint revealed no significant differences in the tissue TMB, blood TMB, and MATH value between the patients who responded to immunotherapy and those who did not. Moreover, no significant differences in the expression percentages of positive immune cells in tumor, stroma, and total regions were identified between the above two groups of patients.ConclusionHNSCC is characterized by high mutation rate, high mutation burden, and high level of immune cell infiltration, and a subset of HNSCC patients respond to immunotherapy. Here, we showed that high mutation burden and immune cell infiltration may improve the prognosis of HNSCC patients with immunotherapy, while there was no remarkable effect on the efficacy.
Highlights
Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it
Immunotherapy is based on immune escape mechanism, and has shown promising prospects in tumor treatment, especially in treating HNSCC patients with recurrence and metastasis; the curative effect of immunotherapy cannot be achieved by traditional therapy [4]
No mutations were found in genes related to Myc pathway, and only 9 signaling pathways were annotated by the Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses, with mutations mainly in the RTK-RAS pathway (Fig. 1C)
Summary
Immunotherapy is an important treatment in oncology, but only a fraction of patients with head and neck squamous cell carcinoma (HNSCC) benefit from it. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors worldwide, with 1.45 million new cases and 500,000 deaths each year [1]. Comprehensive treatment methods such as surgery, chemoradiotherapy, and molecular targeting are commonly used in the treatment of locally advanced patients [2]. Immunotherapy is based on immune escape mechanism, and has shown promising prospects in tumor treatment, especially in treating HNSCC patients with recurrence and metastasis; the curative effect of immunotherapy cannot be achieved by traditional therapy [4]. It is of great significance to screen and identify the relevant biomarkers of immunotherapy efficacy and prognosis of HNSCC patients
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