T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases.
Gigascience
; 122022 12 28.
Article
em En
| MEDLINE
| ID: mdl-37161965
ABSTRACT
BACKGROUND:
Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T-cell infiltration in CLM using T-cell receptor (TCR) repertoire sequencing. Eighty-five resected CLMs from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T-cell fractions were calculated, repertoire clonality was analyzed based on Hill evenness curves, and TCR sequence convergence was assessed using network analysis.RESULTS:
Increased T-cell fractions (10.6% vs. 6.3%) were detected in CLMs exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT-exposed tumors independently of the timing of NACT administration and surgery. While private clones made up >90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence.CONCLUSIONS:
TCR repertoire sequencing can be used to quantify T-cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T-cell clonal expansion in CLM in a clinical context.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Tipos_de_cancer
/
Colon_e_reto
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Neoplasias Hepáticas
Limite:
Humans
Idioma:
En
Revista:
Gigascience
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Noruega