The Immune Cell Composition in Primary Lung Squamous Cell Carcinomas Influences Patterns of Recurrence and Survival

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with squamous cell carcinoma (SCCA) being a prominent histology. Emerging data suggests that immunological parameters have predictive and prognostic value in NSCLC. In this study we determine if the immune cell infiltrate (ICI) in primary lung SCCA tumors influences patterns of recurrence and survival. We retrospectively collected data from an IRB approved prospective tissue collection protocol, which profiled all tumors for gene expression with Affymetrix Hu-RSTA microarray chips (Affymetrix; Santa Clara, CA). We identified tumor samples from patients diagnosed with lung SCCA who underwent surgery between 1997 and 2010. The CIBERSORT deconvolution algorithm was employed to infer the composition of the immune cell infiltrate (22 distinct immune cell types) in tumors via gene expression. ICI presence was dichotomized at the median, where high refers to counts above the median. Time to event analyses were assessed with Kaplan-Meier methods and compared with log rank test. Cox regression was performed to evaluate the effect of predictors on defined outcomes. We identified 258 patients for this analysis. The median age was 70 years (range, 72-88) and the majority (67%) were male and had an ECOG performance status of 1 (65%). The median tobacco pack-years was 50 (range, 0-180), 33% were current and 64% were former smokers. Stages were IA (24%), IB (27%), IIA (8%), IIB (27%) and IIIA/B (14%). Nineteen (7 %) patients received NACT, 17% received adjuvant CT and 9% received adjuvant radiotherapy. The median follow-up time was 19 months with a 2-year OS of 76% and a 2-yr freedom from recurrence of 77%. ICI analysis identified that a high presence of activated CD4+ memory T cells predicts for recurrence in the lung vs other site (77% vs 23%, p = 0.01). Similarly, a high presence of activated NK cells predicts for locoregional recurrence (62% vs 38%, p = 0.03) and high resting NK cells predict for distant recurrence (66% vs 35%, p = 0.02). Predictors for OS were male gender (HR: 1.6, 95% CI 1.1-2.5, p = 0.03), and high presence of resting dendritic cells (HR: 1.5, 95% CI 1.0-2.2, p = 0.04) and eosinophils (HR: 1.6, 95% CI 1.0-2.4, p = 0.03) on multivariable analysis. Our results suggest that the immune cell composition of primary lung SCCA tumors may influence patterns of recurrence. This data may assist with novel means to optimize treatment selection and sequencing.