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Loss of MHC Class I Expression in HPV-associated Cervical and Vulvar Neoplasia: A Potential Mechanism of Resistance to Checkpoint Inhibition.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2020 Sep; Vol. 44 (9), pp. 1184-1191. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Antineoplastic Agents, Immunological adverse effects
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen immunology
Carcinoma, Squamous Cell drug therapy
Carcinoma, Squamous Cell immunology
Carcinoma, Squamous Cell pathology
Down-Regulation
Female
Host-Pathogen Interactions
Humans
Papillomaviridae immunology
Papillomavirus Infections immunology
Papillomavirus Infections pathology
Programmed Cell Death 1 Receptor antagonists & inhibitors
Programmed Cell Death 1 Receptor immunology
Retrospective Studies
Squamous Intraepithelial Lesions of the Cervix drug therapy
Squamous Intraepithelial Lesions of the Cervix immunology
Squamous Intraepithelial Lesions of the Cervix pathology
Uterine Cervical Neoplasms drug therapy
Uterine Cervical Neoplasms immunology
Uterine Cervical Neoplasms pathology
Vulvar Neoplasms drug therapy
Vulvar Neoplasms immunology
Vulvar Neoplasms pathology
Antineoplastic Agents, Immunological therapeutic use
Carcinoma, Squamous Cell virology
Drug Resistance, Neoplasm
Histocompatibility Antigens Class I immunology
Papillomaviridae pathogenicity
Papillomavirus Infections virology
Squamous Intraepithelial Lesions of the Cervix virology
Uterine Cervical Neoplasms virology
Vulvar Neoplasms virology
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 44
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 32496434
- Full Text :
- https://doi.org/10.1097/PAS.0000000000001506