Our data support the potential of CPI in the treatment of PCNSL and suggest several immune checkpoint molecules, including CTLA-4, TIGIT, HAVCR2/TIM-3, and LAG-3, as promising targets that should be evaluated in future prospective clinical studies in the treatment of PCNSL for synergistic effects with new B cell targeting approaches including anti-CD79b antibody-drug conjugates, bispecific T-cell engagers, or CAR T-cell therapies [39]. This evidence concerns the gene TIGIT and primary central nervous system lymphoma.