Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma.

OBJECTIVES: Anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti-PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti-PD-1/PD-L1 immunotherapy-related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti-PD-1/PD-L1 treatment in early-stage SqCLC. METHODS: A total of 255 specimens from patients with early-stage SqCLC were identified within participating centers of the Strategic Partnering to Evaluate Cancer Signatures program. PD-L1 protein expression by immunohistochemistry was evaluated by using the Dako PD-L1 22C3 pharmDx kit on the Dako Link 48 auto-stainer (Dako, Carpinteria, CA). Tumor mutation burden (TMB) was calculated on the basis of data from targeted genome sequencing. The T-effector and interferon gamma (IFN-γ) gene signature was determined from Affymetrix gene chip data (Affymetrix, Santa Clara, CA) from frozen specimens. RESULTS: The prevalence of PD-L1 expression was 9.8% at a tumor proportion score cutoff of at least 50%. PD-L1 mRNA and programmed cell death 1 ligand 2 mRNA positively correlated with PD-L1 protein expression on tumor cells (TCs) and tumor-infiltrating immune cells. PD-L1 protein expression on tumor-infiltrating immune cells was correlated with the T-effector and IFN-γ gene signature (p < 0.001), but not with TMB. For TCs, all of these biomarkers were independent of each other and neither PD-L1 protein expression, TMB, or T-effector and IFN-γ gene signatures were independently prognostic for patient outcomes. CONCLUSIONS: Evaluation of PD-L1 expression, TMB, and T-effector and IFN-γ gene signatures in the cohort with early-stage SqCLC found them to be independent of each other, and none was associated with overall survival. Our results also support the hypothesis that PD-L1 expression is regulated by an intrinsic mechanism on TCs and an adaptive mechanism on immune cells.

Neighborhood-level socioeconomic determinants impact outcomes in nonsmall cell lung cancer patients in the Southeastern United States.

BACKGROUND: Studies examining the impact of lower socioeconomic status (SES) on the outcomes of patients with nonsmall cell lung cancer (NSCLC) are inconsistent. The objective of this study was to clearly elucidate the association between SES, education, and clinical outcomes among patients with NSCLC. METHODS: The study population was derived from a consecutive, retrospective cohort of patients with NSCLC who received treatment within the Duke Health System between 1995 and 2007. SES determinants were based on the individual's census tract and corresponding 2000 Census data. Determinants included the percentage of the population living below poverty, the median household income, and the percentages of residents with at least a high school diploma and at least a bachelor's degree. The SES and educational variables were divided into quartiles. Statistical comparisons were performed using the 25th and 75th percentiles. RESULTS: Individuals who resided in areas with a low median household income or in which a high percentage of residents were living below the poverty line had a shorter cancer-specific 6-year survival than individuals who resided in converse areas (P = .0167 and P = .0067, respectively). Those living in areas in which a higher percentage of residents achieved a high school diploma had improved disease outcomes compared with those living in areas in which a lower percentage attained a high school diploma (P = .0033). A survival advantage also was observed for inhabitants of areas in which a higher percentage of residents attained a bachelor's degree (P = .0455). CONCLUSIONS: Low SES was identified as an independent prognostic factor for poor survival in patients with both early and advanced stage NSCLC. Patients who lived in areas with high poverty levels, low median incomes, and low education levels had worse mortality.