Abstract
Nasopharyngeal carcinoma (NPC) is an EBV-associated epithelial cancer common in the Southern Chinese population. Patients with recurrent or metastatic NPC treated with PD-1 blockade showed a response rate of 20.5%, with no correlation observed between the expression of PD-L1 and treatment response. In an effort to identify biomarkers for anti-PD-1 treatment response, we evaluated a cohort of 10 NPC patients with recurrent or metastatic NPC treated with nivolumab or pembrolizumab. Laser capture microdissection was performed on pretreatment biopsies, with tumor and microenvironment compartments separately microdissected. Nasopharyngeal epithelium from normal nasopharyngeal biopsies were also microdissected as controls. Smart-3SEQ, a novel 3´ end RNA-Seq technique that allows for the accurate quantification of transcript abundance in FFPE samples, was performed to obtain gene expression libraries. ERAP2, a zinc metalloaminopeptidase that performs N-terminal trimming of antigenic epitopes for presentation by MHC class I, was among the most highly upregulated genes in the tumor compartment of nonresponders (adjusted p = 0.033). ERAP2 overexpression was also observed in NPC tumors compared to normal controls. Immunohistochemistry validated the overexpression of ERAP2 in nonresponders, while responders had similar expression to normal controls. In conclusion, ERAP2 is overexpressed in NPC tumors and is a promising biomarker for reduced anti-PD-1 response in NPC.
Citation Format: Joshua K. Tay, Brigette B.Y. Ma, Sushama Varma, Yaw Chyn Lim, Chee Seng Tan, Kwok Wai Lo, John B. Sunwoo, Kevin J. Cullen, Boon Cher Goh, Robert B. West. ERAP2 overexpression is a marker for reduced anti-PD-1 response in nasopharyngeal carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B28.
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