Lymphovascular Invasion Is Associated With Mutational Burden and PD-L1 in Resected Lung Cancer

Background. High tumor mutational burden (TMB) and PD-L1 expression are leading biomarkers in metastatic non-small cell lung cancer (NSCLC) and predict favorable response to checkpoint inhibitors. We sought to identify clinicopathologic characteristics associated with elevated TMB and PD-L1 expression among patients who underwent resection for NSCLC. Methods. NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunogenomic profiling project (ICON). Multiplex immunofluorescence (mIF) quantified densities (cells/mm(2)) of CD3(+), CD3(+)CD8(+), CD3(+)CD8(+)PD-1(+), malignant cells (MCs), MCsPD-L1(+), CD68(+), CD68(+)PD-L1(+), and CD20(+) cells. Whole exome sequencing quantified TMB (mutations/megabase). TMB and MCsPD-L1(+) were dichotomized according to the median of each. Results. A total of 55 patients completed multiplex immunofluorescence and whole-exome sequencing profiling. In this sample, 41.8% (23 of 55) had pathologic stage I disease. Median TMB and MCsPD-L1(+) were 3.91 and 0.62 cells/mm(2), respectively. TMB was higher among smokers (P = .001) and tumors with lymphovascular invasion (LVI) (P = .051). TMB was positively correlated with densities of MCsPD-L1(+) (r = 0.293, P = .030), CD68(+)PD-L1(+) (r = 0.289, P = .033), and CD20(+) (r = 0.310, P = .043) cells. The density of MCsPD-L1(+) was associated with increased CD3(+)CD8(+) (r = 0.319, P = .018) and CD68(+)PDL1(+) (r = 0.371, P = .005) cells. Patients with PD-L1(High)TMB(High) tumors (30.9%, 17 of 55) had higher intratumoral densities of CD3(+), CD3(+)CD8(+), CD68(+), CD68(+)PD-L1(+), and CD20(+) cells. On multivariable analysis LVI was associated with synchronous elevated TMB and PD-L1 expression (odds ratio 3.53, P = .039). Conclusions. NSCLC tumors with elevated TMB and PD-L1 expression are associated with LVI and increased intratumoral immune cell infiltration. These findings may potentially improve patient selection for checkpoint inhibitor therapy trials in the adjuvant setting. (C) 2020 by The Society of Thoracic Surgeons