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Cancer Med ; 13(1): e6844, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38132831

RESUMO

BACKGROUND: T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor, dampens immune function. TIM-3 antagonists have entered the clinic. METHODS: We analyzed TIM-3 transcriptomic expression in 514 diverse cancers. Transcript abundance was normalized to internal housekeeping genes and ranked (0-100 percentile) to a reference population (735 tumors; 35 histologies [high≥75 percentile rank]). Ninety tumors (17.5%) demonstrated high TIM-3 expression. RESULTS: TIM-3 expression varied between and within tumor types. However, high TIM-3 expression was more common in pancreatic cancer (20/55 tumors, 36.4%; odds ratio, 95% confidence interval (pancreatic vs. other tumors) = 3.176 (1.733-5.818; p < 0.001, multivariate]). High TIM-3 also significantly and independently correlated with high PD-L1 (p = 0.014) and high CTLA-4 (p < 0.001) transcriptomic expression (multivariate). CONCLUSIONS: These observations indicate that TIM-3 RNA expression is heterogeneous, but more common in pancreatic cancer and in tumors exploiting PD-L1 and CTLA-4 checkpoints. Clinical trials with patient selection for matched immune-targeted combinations may be warranted.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A , Neoplasias Pancreáticas , Transcriptoma , Humanos , Receptor Celular 2 do Vírus da Hepatite A/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Regulação Neoplásica da Expressão Gênica , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Perfilação da Expressão Gênica , Feminino , Masculino , Heterogeneidade Genética
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