Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma

To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two chest computed tomography (CT)-defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers, and solid density nodules contain invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression, an effector immune response is present but is effectively thwarted by the immune-suppressive elements.

Automated summary

This study investigates the dynamic interaction between the tumor and its tumor microenvironment (TME) during lung cancer progression. Gene alterations in the extracellular matrix and fibroblasts are central in the preinvasive state. T-cell mediated immune suppression is initiated in preinvasive nodules and intensifies through progression to invasive tumors. Reduced T cell infiltration is more commonly associated with preinvasive cancers, while upregulation of immune checkpoints occurs only in invasive nodules. While an effector immune response is present throughout progression, it is effectively thwarted by immune-suppressive elements.