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Physical interaction with antigen presenting cells primes a T helper tumor lineage

ABSTRACT: Cellular interactions in the tumor microenvironment (TME) drive T cell effector function, or dysfunction, and define a primary mechanism to target anti-tumor T cell immunity. Currently, the interactions that shape T cell function in the TME remain poorly understood. Here, we mapped the molecular programs of T and antigen-presenting cell interactions in human early non-small cell lung carcinoma lesions by physically interacting cell (PIC) sequencing. PIC-seq and imaging identified that in the TME, but not normal lung, PICs are enriched in clonally expanded CD4+PD-1+CXCL13+ T cells, expressing a unique combination of checkpoint molecules, transcription-factors, and cytokines, defining a novel T helper tumor-specific (Tht) program, conserved across cancer types. In vitro and in vivo genetic models of antigen specificity confirmed that the Tht prevalence in TME PICs is driven by tumor-antigen presentation of dendritic cells. Our study highlights CD4+ T-dendritic cell physical interaction as a key factor regulating the TME.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE160903 | GEO | 2022/01/11

REPOSITORIES: GEO

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