Tertiary Lymphoid Structure and CD8 T Cell Exclusion in Minimally Invasive Adenocarcinoma
Posted 04 Aug 2020
medRxiv DOI: 10.1101/2020.08.03.20166991
Posted 04 Aug 2020
Lung adenocarcinoma is the leading cause of cancer death. To characterize the tumor microenvironment (TME) of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 59 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal lung tissues from Chinese patients. We observed mucin over-expression and glycosylation, and altered cytokine-cytokine interactions in MIA tumors, which also had distinct adaptive immune TME of higher CD4+ T cell infiltration, higher plasma B cell activation, and lower CD8+ T cell infiltration. The high expression of markers for B cells, activated CD4 T cells, and follicular helper T (Tfh) cells in MIA implicated the formation of tertiary lymphoid structures (TLS), which were supported by two independent single-cell RNA-seq data. Multiplex immunohistochemistry (mIHC) staining of 22 MIA tumors validated TLS formation and revealed an enrichment of follicular regulatory T cells (Tfr) in TLS follicles, which may explain the lower CD8+ T cell infiltration and attenuated anti-tumor immunity in MIA.
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