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Lymphovascular Invasion Is Associated With Mutational Burden and PD-L1 in Resected Lung Cancer.
- Source :
- Annals of Thoracic Surgery; Feb2020, Vol. 109 Issue 2, p358-366, 9p
- Publication Year :
- 2020
-
Abstract
- High tumor mutational burden (TMB) and programmed death ligand 1 (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. NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunogenomic profiling project. Multiplex immunofluorescence quantified densities (cells/mm<superscript>2</superscript>) of CD3<superscript>+</superscript>, CD3<superscript>+</superscript>CD8<superscript>+</superscript>, CD3<superscript>+</superscript>CD8<superscript>+</superscript>PD-1<superscript>+</superscript>, malignant cells (MCs), MCsPD-L1<superscript>+</superscript>, CD68<superscript>+</superscript>, CD68<superscript>+</superscript>PD-L1<superscript>+</superscript>, and CD20<superscript>+</superscript> cells. Whole-exome sequencing quantified TMB (mutations/megabase). TMB and MCsPD-L1<superscript>+</superscript> were dichotomized according to the median of each. 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<superscript>+</superscript> were 3.91 and 0.62 cells/mm<superscript>2</superscript>, 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<superscript>+</superscript> (r = 0.293, P =.030), CD68<superscript>+</superscript>PD-L1<superscript>+</superscript> (r = 0.289, P =.033), and CD20<superscript>+</superscript> (r = 0.310, P =.043) cells. The density of MCsPD-L1<superscript>+</superscript> was associated with increased CD3<superscript>+</superscript>CD8<superscript>+</superscript> (r = 0.319, P =.018) and CD68<superscript>+</superscript>PD-L1<superscript>+</superscript> (r = 0.371, P =.005) cells. Patients with PD-L1<superscript>High</superscript>TMB<superscript>High</superscript> tumors (30.9%, 17 of 55) had higher intratumoral densities of CD3<superscript>+</superscript>, CD3<superscript>+</superscript>CD8<superscript>+</superscript>, CD68<superscript>+</superscript>, CD68<superscript>+</superscript>PD-L1<superscript>+</superscript>, and CD20<superscript>+</superscript> cells. On multivariable analysis LVI was associated with synchronous elevated TMB and PD-L1 expression (odds ratio 3.53, P =.039). 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00034975
- Volume :
- 109
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Annals of Thoracic Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 141322160
- Full Text :
- https://doi.org/10.1016/j.athoracsur.2019.08.029