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

Nasser K. Altorki, Alain C. Borczuk, Sebron Harrison, Lauren K. Groner, Bhavneet Bhinder, Vivek Mittal, Olivier Elemento, Timothy E. McGraw

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number110639
JournalCell Reports
Volume39
Issue number1
DOIs
StatePublished - Apr 5 2022

Keywords

  • CP: Cancer
  • CT scan density
  • extracellular matrix
  • GGO
  • lung ground glass lesions
  • preinvasive lung adenocarcinoma
  • Tregs
  • tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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