Dataset Information

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

ABSTRACT:

Background

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.

Methods

NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunogenomic profiling project. Multiplex immunofluorescence quantified densities (cells/mm²) 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/mm², 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⁺PD-L1⁺ (r = 0.371, P = .005) cells. Patients with PD-L1^HighTMB^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.

SUBMITTER: Mitchell KG

PROVIDER: S-EPMC7366360 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Mitchell Kyle G KG Negrao Marcelo V MV Parra Edwin R ER Li Jun J Zhang Jianhua J Dejima Hitoshi H Vaporciyan Ara A AA Swisher Stephen G SG Weissferdt Annikka A Antonoff Mara B MB Cascone Tina T Roarty Emily E Wistuba Ignacio I II Heymach John V JV Gibbons Don L DL Zhang Jianjun J Sepesi Boris B

The Annals of thoracic surgery 20190921 2

<h4>Background</h4>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.<h4>Methods</h4>NSCLC patients undergoing primary resection (2016-2018) were prospectively enrolled in an immunog ...[more]

PMID: 31550464

Similar Datasets

Project description:BackgroundImmunotherapy using programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors seems less effective in non-small cell lung cancer (NSCLC) patients with epithelial growth factor receptor (EGFR) mutations. Varied responses to PD-1/PD-L1 inhibitors have recently been observed in NSCLC patients harboring different types of EGFR mutations. Some EGFR-mutated NSCLC patients may benefit from PD-1/PD-L1 inhibitors. At present, PD-L1 expression, tumor mutational burden (TMB), and tumor immune microenvironment (TIME) are biomarkers for predicting the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients. We retrospectively evaluated PD-L1 expression, TMB, and immune cell infiltration in NSCLC patients with EGFR mutation subtypes.MethodsPD-L1 expression, TMB, and the abundance of immune cell infiltration in NSCLC patients were evaluated in public databases and clinical samples. TMB was detected using the NGS technique, PD-L1 was detected using immunohistochemistry, and the abundance of immune cell infiltration in NSCLC samples was detected using multiple immunohistochemistry.ResultsPD-L1 expression and TMB were lower in EGFR-mutated NSCLCs than in wild-type patients. Differences in the abundance of immune cell infiltration were also observed between EGFR-mutated and wild-type NSCLC. The expression of PD-L1, TMB, and abundance of immune cell infiltration were different in patients harboring different subtypes of EGFR mutations. Patients with uncommon EGFR mutations, especially the G719X mutation, showed higher TMB and expressions of PD-L1 than classical EGFR mutations. M1 macrophages were higher in uncommon EGFR mutations than classical EGFR mutations.ConclusionsThe expression of PD-L1 and TMB in uncommon EGFR-mutated NSCLCs, especially the G719X mutation, were higher than those for classical EGFR-mutated NSCLCs and similar to EGFR wild-type. The abundance of immune cell infiltration in uncommon EGFR-mutated NSCLCs was similar to that in EGFR wild-type. Our findings suggest that uncommon EGFR-mutated NSCLCs may benefit from PD-1/PD-L1 inhibitors.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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