1. Pan-cancer analysis of TIM-3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity.
- Author
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Jungah Lim, Kurzrock, Razelle, Daisuke Nishizaki, Hirotaka Miyashita, Adashek, Jacob J., Lee, Suzanna, Pabla, Sarabjot, Nesline, Mary, Conroy, Jeffrey M., DePietro, Paul, Lippman, Scott M., and Shumei Kato
- Subjects
PANCREATIC tumors ,HEPATITIS A virus cellular receptors ,GENE expression ,PANCREATIC cancer ,IMMUNE checkpoint proteins ,TRANSCRIPTOMES - Abstract
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 PDL1 and CTLA-4 checkpoints. Clinical trials with patient selection for matched immune-targeted combinations may be warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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