Phosphorylation of SMAD3 in immune cells predicts survival of patients with early stage non-small cell lung cancer

Sebastian Marwitz, Carmen Ballesteros-Merino, Shawn M. Jensen, Martin Reck, Christian Kugler, Sven Perner, Daniel Drömann, Torsten Goldmann, Bernard A. Fox

2 Citations (Scopus)


Background The interplay of immune and cancer cells takes place in the tumor microenvironment where multiple signals are exchanged. The transforming growth factor beta (TGFB) pathway is known to be dysregulated in lung cancer and can impede an effective immune response. However, the exact mechanisms are yet to be determined. Especially which cells respond and where does this signaling take place with respect to the local microenvironment. Methods Human non-small cell lung cancer samples were retrospectively analyzed by multiplexed immunohistochemistry for SMAD3 phosphorylation and programmed death ligand 1 expression in different immune cells with respect to their localization within the tumor tissue. Spatial relationships were studied to examine possible cell-cell interactions and analyzed in conjunction with clinical data. Results TGFB pathway activation in CD3, CD8, Foxp3 and CD68 cells, as indicated by SMAD3 phosphorylation, negatively impacts overall and partially disease-free survival of patients with lung cancerindependent of histological subtype. A high frequency of Foxp3 regulatory T cells positive for SMAD3 phosphorylation in close vicinity of CD8 T cells within the tumor discriminate a rapidly progressing group of patients with lung cancer. Conclusions TGFB pathway activation of local immune cells within the tumor microenvironment impacts survival of early stage lung cancer. This might benefit patients not eligible for targeted therapies or immune checkpoint therapy as a therapeutic option to re-activate the local immune response.

Original languageEnglish
Article numbere001469
JournalJournal for ImmunoTherapy of Cancer
Issue number2
Publication statusPublished - 15.02.2021

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Research Area: Luebeck Integrated Oncology Network (LION)
  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)


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