Distinct phenotypic states and spatial distribution of CD8 + T cell clonotypes in human brain metastases.
> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)
书目信息
作者摘要（按来源许可复用）
Metastatic disease in the brain is difficult to control and predicts poor prognosis. Here, we analyze human brain metastases and demonstrate their robust infiltration by CD8 + T cell subsets with distinct antigen specificities, phenotypic states, and spatial localization within the tumor microenvironment. Brain metastases are densely infiltrated by T cells; the majority of infiltrating CD8 + T cells express PD-1. Single-cell RNA sequencing shows significant clonal overlap between proliferating and exhausted CD8 + T cells, but these subsets have minimal clonal overlap with circulating and other tumor-infiltrating CD8 + T cells, including bystander CD8 + T cells specific for microbial antigens. Using spatial transcriptomics and spatial T cell receptor (TCR) sequencing, we show these clonally unrelated, phenotypically distinct CD8 + T cell populations occupy discrete niches within the brain metastasis tumor microenvironment. Together, our work identifies signaling pathways within CD8 + T cells and in their surrounding environment that may be targeted for immunotherapy of brain metastases.
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