A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer

• DOI: 10.1038/s41467-022-35238-w
• Publication Date: 2023-01-06T12:07:37Z
• Authors: Sandra Tietscher; Johanna Wagner; Tobias Anzeneder; Claus Langwieder; Martin Rees; Bettina Sobottka; Natalie de Souza; Bernd Bodenmiller
• Keywords: Immune checkpoint; Mass cytometry; CXCL13

Abstract Immune checkpoint therapy in breast cancer remains restricted to triple negative patients, and long-term clinical benefit is rare. The primary aim of immune blockade prevent or reverse exhausted T cell states, but exhaustion tumors not well understood. Here, we use single-cell transcriptomics combined with imaging mass cytometry systematically study environments human that either do contain cells, a focus on luminal subtypes. We find the presence PD-1 high exhaustion-like phenotype associated an inflammatory environment characteristic cytotoxic profile, increased myeloid activation, evidence for elevated immunomodulatory, chemotactic, cytokine signaling, accumulation natural killer cells. Tumors harboring exhausted-like cells show expression MHC-I tumor CXCL13 as altered spatial organization more immature rather than mature tertiary lymphoid structures. Our data reveal fundamental differences between without within cancer, – PD-L1 are strong distinguishing features these environments.