Loss of MHC Class I Expression in HPV-associated Cervical and Vulvar Neoplasia

MHC I级 外阴上皮内瘤变 主要组织相容性复合体 免疫学 生物 癌症研究 医学 抗原 病理 外阴
作者
Megan E. Dibbern,Timothy N. J. Bullock,Taylor M. Jenkins,Linda Duska,Mark H. Stoler,Anne M. Mills
出处
期刊:The American Journal of Surgical Pathology [Lippincott Williams & Wilkins]
卷期号:44 (9): 1184-1191 被引量:21
标识
DOI:10.1097/pas.0000000000001506
摘要

Tumor cell expression of major histocompatibility complex (MHC) class I is required for antigen presentation and adaptive immune recognition. Absent or diminished MHC class I expression is thought to contribute to immunotherapeutic resistance in some epithelial tumors but has not been previously studied in cervical and vulvar carcinoma. Given that anti–programmed cell death 1 (PD-1) checkpoint inhibition is deployed for programmed cell death ligand 1 (PD-L1)-positive recurrent and metastatic cervical squamous carcinomas, identifying tumors with loss of MHC class I is of clinical interest to optimize the selection of immunotherapeutic candidates. Immunohistochemistry for PD-L1 and MHC class I combined A, B, and C heavy chains (MHC class I) was assessed in 58 human papillomavirus–associated cervical and vulvar lesions, including 27 squamous intraepithelial lesions (SILs) and 31 invasive squamous cell carcinoma (SCC). Although 84% of SCC and 22% of SIL were PD-L1-positive, 35.5% (11/31) of SCC and 18.5% (5/27) of SIL also showed clonal or complete loss of MHC class I. Loss of MHC class I expression was more common in PD-L1-positive (10/26, 38%) versus PD-L1-negative SCC (1/5, 20%). In summary, over one third of human papillomavirus–associated cervical and vulvar SCC show clonal or complete loss of MHC class I expression, including many PD-L1-positive cases. This suggests that the efficacy of checkpoint inhibitors targeting the PD-1/PD-L1 axis may be limited in a subset of cervical and vulvar squamous neoplasms due to an impaired ability to engage with the adaptive immune system related to loss of MHC class I expression.
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