Tumour-Associated Neutrophils: An H&E-Based Biomarker Predicting Patient Outcomes to Anti-Pd-1 Monotherapy in Lung Adenocarcinoma
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Authors
Choi, Angela
Date
Type
thesis
Language
eng
Keyword
Lung cancer , Immunotherapy , Biomarker , Tumour-associated neutrophils
Alternative Title
Abstract
Purpose: Immune checkpoint blockades are the standard of care for advanced non-small cell lung cancers. Patients with high PD-L1 expression on tumour cells receive anti-PD-1 monotherapy as a first-line treatment. However, more than half of the patients do not respond to the therapy, which demonstrates potential limitations of the current PD-L1 biomarker. Novel biomarkers to identify this treatment-resistant subset of non-small cell lung cancers are needed. Hypothesis: We hypothesize that assessing tumour-associated neutrophil (TAN) in the pre-treatment tumour immune microenvironment will improve prediction of patient clinical outcomes to anti-PD-1 therapy in non-small cell lung cancer. Aim 1: Determine if TAN is a biomarker that associates with response and/or survival in patients with PD-L1high lung adenocarcinomas receiving anti-PD-1 monotherapy. Aim 2: In the PD-L1high cohort, characterize TAN prevalence and survival associations in relation to patient demographics and emerging biomarkers in non-small cell lung cancer. Aim 3: In patients with PD-L1low lung adenocarcinomas receiving combination therapy, evaluate prevalence and clinical outcome associations with TAN. Methodology: Archival diagnostic lung adenocarcinoma specimens assessed for PD-L1 expression were collected. Patients with PD-L1high lung adenocarcinomas were prospectively allocated into discovery (n=27) and validation (n=28) cohorts. A cohort of PD-L1low patients (n=34) was also established. Routine clinical H&E slides were visually assessed for TAN. Results: TAN(+) cases were associated with significantly poor overall survival in both discovery and validation PD-L1high cohorts (p=0.0469 and p=0.0246, respectively). In relation to clinicopathological features, TAN(+) lung adenocarcinomas was independently associated with poor overall survival. The same significant associations were not observed in the PD-L1low cohort.
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Attribution 4.0 International
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.