Abstract 206P
Background
Small cell lung cancer (SCLC) is characterized by early metastatic potential and poor prognosis. Liver kinase B1 (LKB1) is a cell metabolism regulator and oncosuppressor. LKB1 downregulation has been associated with a cold tumor immune microenvironment (TIME). We aimed to analyze the role of LKB1 in SCLC in relation to TIME components and its association with overall survival (OS).
Methods
We retrospectively evaluated SCLC patients (pts) consecutively treated at our Institution from 1996 to 2020 and with available tissue. LKB1, PD-L1 (22C3) on tumor cells and on tumor immune-infiltrating cells, CD8 and FOXP3 were evaluated by immunohistochemistry (IHC). IHC scores were then categorized.
Results
138 SCLC pts were included. 80 pts (58.0%) had limited stage (LS) at diagnosis and were treated with radical chemoradiotherapy (n = 31, 22.5%) or surgery followed by adjuvant chemotherapy (ChT; n = 49, 35.5%). 58 pts (42.0%) presented with extended stage (ES) and were treated with ChT. Median LKB1 IHC score was 4 (range 0–18). 67 pts (48.5%) were classified as LKB1-positive (IHC score > 4). A significantly higher proportion of pts diagnosed with LS showed LKB1 positive status (58.8% vs 34.5% of pts with ES; p = 0.005). Multivariate analysis (MVA) confirmed the significant correlation of LKB1 status and LS. At data cut-off (January 2, 2024), 123 pts (89.1%) died. Median OS (mOS) was 14.0 months (mos; 95% confidence interval [95%CI] 11.5–19.4). mOS was significantly longer in pts with LKB1 positive vs negative expression (32.4 mos [95%CI 13.6–62.4] vs 11.2 mos [95%CI 8.7–14.7]; p < 0.001). At MVA, positive LKB1 expression, LS and no weight loss at diagnosis were confirmed as independent positive prognostic factors. TIME features were evaluated in 70 pts. LKB1 expression was negatively correlated to the presence of CD8+ tumor infiltrating lymphocytes (TILs; p = 0.013). No correlation was found between LKB1 and PD-L1 expression nor the presence of FOXP3+ TILs.
Conclusions
LKB1 expression is a potential positive prognostic marker in SCLC. In this series, LKB1 expression was negatively associated with the presence of CD8+ TILs. Future studies will evaluate pts treated with chemoimmunotherapy and expand TIME analysis.
Legal entity responsible for the study
Istituto Oncologico Veneto IOV – IRCCS.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.