HAVCR2 and neoplasm: Lim and June (2017) suggested that the TME of solid tumors is hostile for CAR-T cells, reporting that even though CAR-T cells successfully penetrate into the tumor, they are exposed to numerous suppressive factors and tumor-associated stromal cells, which contribute to limiting their function. Additionally, these infused CAR-T cells express high levels of PD-1, T-cell immunoglobulin domain and mucin domain protein 3 (TIM3) and CTLA-4, indicating that they become exhausted or dysfunctional cells (Lim and June, 2017).