Germline HLA landscape does not predict efficacy of pembrolizumab monotherapy across solid tumor types.
Immunity
; 55(1): 56-64.e4, 2022 01 11.
Article
en En
| MEDLINE
| ID: mdl-34986342
ABSTRACT
We evaluated the impact of class I and class II human leukocyte antigen (HLA) genotypes, heterozygosity, and diversity on the efficacy of pembrolizumab. Seventeen pembrolizumab clinical trials across eight tumor types and one basket trial in patients with advanced solid tumors were included (n > 3,500 analyzed). Germline DNA was genotyped using a custom genotyping array. HLA diversity (measured by heterozygosity and evolutionary divergence) across class I loci was not associated with improved response to pembrolizumab, either within each tumor type evaluated or across all patients. Similarly, HLA heterozygosity at each class I and class II gene was not associated with response to pembrolizumab after accounting for the number of tests conducted. No conclusive association between HLA genotype and response to pembrolizumab was identified in this dataset. Germline HLA genotype or diversity alone is not an important independent determinant of response to pembrolizumab and should not be used for clinical decision-making in patients treated with pembrolizumab.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Mutación de Línea Germinal
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Anticuerpos Monoclonales Humanizados
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Inhibidores de Puntos de Control Inmunológico
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Genotipo
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Antígenos HLA
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Neoplasias
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Año:
2022
Tipo del documento:
Article