CD4 and central nervous system cancer: In contrast, the most used chemotherapeutic to treat glioblastoma patients, temozolomide, when administered at a high dose schedule (50 mg/kg daily for 5 days) into mice bearing GL261 and KR158 murine glioma models led to an upregulation of exhaustion markers LAG-3 and TIM-3 on CD4+ and CD8+ T cells [131].