Pan‐cancer analysis of TIM‐3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity

Abstract

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 PD‐L1 and CTLA‐4 checkpoints. Clinical trials with patient selection for matched immune‐targeted combinations may be warranted.