Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes.
Oncoimmunology
; 13(1): 2345859, 2024.
Article
em En
| MEDLINE
| ID: mdl-38686178
ABSTRACT
Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRß) repertoire dynamics contribute to the therapeutic response. Using murine models that exclude variation in host genetics, environmental factors and tumour mutation burden, limiting variation between animals to naturally diverse TCRß repertoires, we applied TCRseq, single cell RNAseq and flow cytometry to study TCRß repertoire dynamics in ICT responders and non-responders. Increased oligoclonal expansion of TCRß clonotypes was observed in responding tumours. Machine learning identified TCRß CDR3 signatures unique to each tumour model, and signatures associated with ICT response at various timepoints before or during ICT. Clonally expanded CD8+ T cells in responding tumours post ICT displayed effector T cell gene signatures and phenotype. An early burst of clonal expansion during ICT is associated with response, and we report unique dynamics in TCRß signatures associated with ICT response.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos do Interstício Tumoral
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Receptores de Antígenos de Linfócitos T alfa-beta
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Inibidores de Checkpoint Imunológico
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Oncoimmunology
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália