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Review
. 2023 Feb 23;13(5):862.
doi: 10.3390/diagnostics13050862.

Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

Piero Giuseppe Meliante  1 , Federica Zoccali  1 , Marco de Vincentiis  1 , Massimo Ralli  1 , Carla Petrella  2 , Marco Fiore  2 , Antonio Minni  1   3 , Christian Barbato  2
Affiliations
Review

Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma

Piero Giuseppe Meliante et al. Diagnostics (Basel). .

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.

Keywords: PD-1/PD-L1; chemotherapy; head and neck squamous cell carcinoma; immunotherapy; immunotherapy molecular marker; immunotherapy resistance; nivolumab; pembrolizumab.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Interferon-related PD-L1 expression in cancer cells.
See this image and copyright information in PMC

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