Based on recent studies on cancer immunotherapy-related cognitive impairments (CRCI) [48, 69, 70], our previous reports [23, 25, 26], and results from the current study, we propose three potential approaches to mitigate ICI-based CRCIs: (i) microglia depletion (ii) selective inhibition of microglial activation using Syk (kinase) inhibitors, or (iii) complement cascade blockade. The gene discussed is SYK; the disease is cancer.