Building on their previous finding that supercentenarians possess a high fraction of CD4+ cytotoxic T cells (CD4+ CTLs) among their peripheral blood mononuclear cells (PBMCs), Hashimoto et al. now show that this unusual and rare subset of T cells, which possess the ability to kill tumour cells in a major histocompatibility complex class II (MHC II)-dependent manner in a range of cancer types, may contribute to cancer suppression.
The authors began by profiling the transcriptome, surface proteins and T cell receptor (TCR) sequences of single T cells from the blood of donors in three age categories: aged 70–90, centenarians and supercentenarians. This revealed a consistent expansion in the proportion of CD4+ CTLs with age. However, this expansion was not specific to supercentenarians, with the highest proportion of CD4+ CTLs observed in a donor under the age of 100, indicating that CD4+ CTL expansion can also take place in younger individuals. Validating their finding, subsequent analysis of public single-cell datasets across a broad age range of 0 to 110 also showed that this immune cell population significantly increased at very advanced ages while remaining at a lower level in younger individuals.
