A large body of evidence indicates that the immune microenvironment controls tumour development. Primary central nervous system lymphomas (PCNSL) are aggressive tumours growing in the central nervous system (CNS). To evaluate the role and characteristics of this immune-privileged site in anti-tumour defences, we compared the cellular and molecular immune microenvironments of growing murine lymphoma B cells injected into the brain or the spleen. In the brain, immune cells, including dendritic cells and T lymphocytes with a large proportion of CD4+forkhead box P3 (FoxP3+) regulatory T cells, rapidly infiltrated the tumour microenvironment. These populations also increased in number in the spleen. The T cell cytokine profiles in tumour-bearing mice were similar in the two sites, with predominant T helper type 1 (Th1)/Th17 polarization after polyclonal stimulation, although some interleukin (IL)-4 could also be found. We demonstrated that these T cells have anti-tumour activity in the CNS, although less than in the spleen: nude mice that received lymphoma cells intracerebrally died significantly earlier than immunocompetent animals. These results demonstrate that the brain is able to recruit all the major actors to mount a specific anti-tumour immune response against lymphoma.