MHC class I loss in endometrial carcinoma: a potential resistance mechanism to immune checkpoint inhibition.
Mod Pathol
; 34(3): 627-636, 2021 03.
Article
em En
| MEDLINE
| ID: mdl-33011747
ABSTRACT
Major histocompatibility complex (MHC) class I is a membrane-bound protein complex expressed on nucleated human cells. MHC class I presents intracellular protein fragments to cytotoxic T cells and triggers an activation cascade upon neoantigen detection by these cells. MHC class I loss by tumor cells decreases tumor neoantigen presentation to the immune system and therefore represents a possible mechanism of immunotherapeutic resistance even among cancers that otherwise appear to be good candidates for checkpoint inhibition, such as mismatch repair (MMR)-deficient and PD-L1-positive malignancies. We herein assess MHC class I expression in a range of endometrial carcinomas, including MMR-deficient and PD-L1-positive cancers. Immunohistochemical staining for combined MHC class I A-, B-, and C-heavy chains was performed on 76 cases of endometrial carcinoma and was classified as present, subclonally lost, or diffusely lost. Tumoral PD-L1 expression, PD-L1 combined positive score, and CD3-positive T lymphocytes were also quantified. Forty-two percent of tumors showed loss of MHC class I expression, either in a subclonal (26%) or diffuse (16%) pattern. This included 46% of MMR-deficient and 25% of PD-L1-positive cancers. These findings suggest that tumoral MHC class I status may be an important factor to consider when selecting endometrial cancer patients for checkpoint inhibition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma
/
Antígenos de Histocompatibilidade Classe I
/
Biomarcadores Tumorais
/
Neoplasias do Endométrio
/
Resistencia a Medicamentos Antineoplásicos
/
Antígeno B7-H1
/
Inibidores de Checkpoint Imunológico
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article