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Updated: Aug 7, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma
Piero Giuseppe Meliante1, Federica Zoccali1, Marco de Vincentiis1
1Department of Sense Organs, Sapienza University of Rome, 00161 Roma, Italy.
Abstract:
Programmed cell death ligand-1 (PD-L1) binds PD-1 on CD8+ lymphocytes, inhibiting their cytotoxic action. Its aberrant expression by head and neck squamous cell carcinoma (HNSCC) cells leads to immune escape. Pembrolizumab and nivolumab, two humanized monoclonal antibodies against PD-1, have been approved in HNSCC treatment, but ~60% of patients with recurrent or metastatic HNSCC fail to respond to immunotherapy and only 20 to 30% of treated patients have long-term benefits. The purpose of this review is to analyze all the fragmentary evidence present in the literature to identify what future diagnostic markers could be useful for predicting, together with PD-L1 CPS, the response to immunotherapy and its durability. We searched PubMed, Embase, and the Cochrane Register of Controlled Trials and we summarize the evidence collected in this review. We confirmed that PD-L1 CPS is a predictor of response to immunotherapy, but it should be measured across multiple biopsies and repeatedly over time. PD-L2, IFN-γ, EGFR, VEGF, TGF-β, TMB, blood TMB, CD73, TILs, alternative splicing, tumor microenvironment, and some macroscopic and radiological features are promising predictors worthy of further studies. Studies comparing predictors appear to give greater potency to TMB and CXCR9.
Insights
Predicting immunotherapy response in head and neck cancer is crucial. This review explores biomarkers beyond PD-L1 CPS to improve patient selection for better treatment outcomes and durable benefits.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Programmed cell death ligand-1 (PD-L1) binding PD-1 inhibits CD8+ T-cell activity, facilitating immune escape in head and neck squamous cell carcinoma (HNSCC).
- While PD-1 inhibitors like pembrolizumab and nivolumab show efficacy, a significant portion of recurrent or metastatic HNSCC patients exhibit resistance or lack long-term benefits.
Purpose of the Study:
- To systematically review existing literature and identify potential diagnostic markers for predicting immunotherapy response and durability in HNSCC.
- To supplement the established PD-L1 Combined Positive Score (CPS) with novel biomarkers for enhanced patient stratification.
Main Methods:
- Comprehensive literature search across PubMed, Embase, and Cochrane Register of Controlled Trials.
- Analysis and synthesis of fragmented evidence on various potential predictive biomarkers for immunotherapy response.
Main Results:
- PD-L1 CPS is confirmed as a response predictor but necessitates multi-biopsy and longitudinal assessment.
- Promising biomarkers include PD-L2, IFN-γ, EGFR, VEGF, TGF-β, Tumor Mutational Burden (TMB), blood TMB, CD73, Tumor-Infiltrating Lymphocytes (TILs), alternative splicing, tumor microenvironment characteristics, and radiological features.
- Comparative studies suggest TMB and CXCR9 may offer superior predictive power.
Conclusions:
- Current PD-L1 CPS assessment requires refinement for optimal utility in HNSCC immunotherapy.
- A multi-marker approach integrating PD-L1 CPS with novel biomarkers like TMB and CXCR9 is essential for improving prediction of immunotherapy response and durability.
- Further research validating these promising biomarkers is warranted to guide clinical decision-making and personalize HNSCC treatment.
