TY - JOUR
T1 - Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis.
AU - Milione, Massimo
AU - Boeri, Mattia
AU - Cantarutti, Anna
AU - Centonze, Giovanni
AU - Busico, Adele
AU - Suatoni, Paola
AU - Garzone, Giovanna
AU - Cattaneo, Laura
AU - Tamborini, Elena
AU - Perrone, Federica
AU - Mangogna, Alessandro
AU - Corrao, Giovanni
AU - Pruneri, Giancarlo
AU - Sozzi, Gabriella
AU - Anichini, Andrea
AU - Pastorino, Ugo
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Almost 25LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a "low inflammatory profile" subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88risk profiles (p textless 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation.
AB - Almost 25LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a "low inflammatory profile" subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88risk profiles (p textless 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation.
KW - inflammation
KW - immune profile
KW - never-smokers
U2 - 10.3390/cancers12071828
DO - 10.3390/cancers12071828
M3 - Article
VL - 12
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 7
ER -