Abstract
The purpose of this study was to evaluate the prognostic impact of major histocompatibility complex (MHC) class I expression and programmed death-ligand 1 (PD-L1) expression in patients with head and neck squamous cell carcinoma (HNSCC). A total of 158 patients with HNSCC were evaluated retrospectively. The expression of MHC class I and PD-L1 was analyzed in tumor specimens using immunohistochemistry. The association between MHC class I/PD-L1 expression and clinical outcome was evaluated by Kaplan-Meier and Cox regression analyses. Among 158 patients, 103 (65.2%) showed positive PD-L1 expression, and 20 (12.7%) showed no detectable expression of MHC class I. The frequency of PD-L1 positive expression with concomitant MHC class I loss was 7.0%. In the PD-L1-positive group, MHC class I loss was associated with a significantly worse survival compared with MHC class I positivity (median overall survival 39.3 months vs. not reached; P = 0.005), whereas MHC class I status provided no prognostic impact in the PD-L1 negative group. Neither PD-L1 nor MHC class I alone showed a significant difference in overall survival. The loss of MHC class I expression in PD-L1-positive HNSCC was associated with a poor clinical outcome. This suggested that MHC class I expression status might be useful for the prognosis of tumor progression in HNSCC when combined with PD-L1 expression status. External validation with enough numbers of participants in such subgroup should be needed for validation.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world[1] and is a heterogeneous disease entity arising from various anatomic sites, including the oral cavity, oropharynx, hypopharynx, and larynx
It is well established that tumor cells often harbor a loss or down-regulation of the major histocompatibility complex (MHC) class I molecules on their surface, and this is considered an immune escape mechanism of the tumor[9]
MHC class I loss has been reported in several types of tumors ranging from 15% to 96%12,13,18,19, few studies have assessed the proportion of concomitant expression of MHC class I and programmed death-ligand 1 (PD-L1), whereas some have analyzed a single parameter’s expression and relation with immune cell infiltration only[20,21,22]
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world[1] and is a heterogeneous disease entity arising from various anatomic sites, including the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 expression was found to be positively correlated with ORR and PFS, suggesting that PD-L1 expression might be a positive predictive marker in some tumors[6,7] Despite these encouraging results, a significant portion of PD-L1-positive patients with advanced HNSCC do not respond to these immune checkpoint inhibitors (ICIs)[8]. A significant portion of PD-L1-positive patients with advanced HNSCC do not respond to these immune checkpoint inhibitors (ICIs)[8] This suggests that there exist additional escape mechanisms that allow tumor cells blocked by ICIs to avoid attack by cytotoxic T lymphocytes. MHC class I loss is a frequent event and is thought to confer a tumor escape function, little is known about its clinical significance in PD-L1-positive patients with HNSCC. We sought to explore the prognostic significance of impaired antigen presentation caused by MHC I loss combined with positive PD-L1 expression
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