摘要：SummaryKnowledge of the tumor microenvironment (TME) in patients with early lung cancer, especially in comparison with the matched adjacent tissues, remains lacking. To characterize TME of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal tissues. MIA tumors exhibited an adaptive TME characterized by high CD4+T cell infiltration, high B-cell activation, and low CD8+T cell infiltration. The high expression of markers for B cells, activated CD4+T cells, and follicular helper T (Tfh) cells in bulk MIA samples and three independent single-cell RNA-seq datasets implied tertiary lymphoid structures (TLS) formation. Multiplex immunohistochemistry staining 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. Our study demonstrates how integrating transcriptome and pathology characterize TME and elucidate potential mechanisms of tumor immune evasion.Graphical abstractDisplay OmittedHighlights•Higher infiltration and activation of B and CD4+T cell characterize MIA tumors•MIA tumors are infiltrated with lower CD8+T cells than normal tissues•TLS constituted by B, CD4+T cells, and CD35+FDC is validated in MIA tumors•Decreased CD8+T is associated with Tfr-mediated immunosuppression in MIA tumorImmunity; Components of the immune system; Cancer
