PD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC.
Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC.



A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression.



Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36-0.94, p = 0.031; HR 0.46, 95%CI 0.26-0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50-0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%).



PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.
Department of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia.
Malaka
M
Ameratunga
Department of Pathology, Austin Health, Victoria, Australia.
Khashayar
K
Asadi
Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canada.
Xihui
X
Lin
The Olivia Newton-John Cancer Research Institute, Victoria, Australia.
Marzena
M
Walkiewicz
Department of Pathology, Austin Health, Victoria, Australia.|The Olivia Newton-John Cancer Research Institute, Victoria, Australia.
Carmel
C
Murone
Department of Thoracics, Austin Health, Victoria, Australia.
Simon
S
Knight
Department of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia.
Paul
P
Mitchell
Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Canada.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
Paul
P
Boutros
Department of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia.|The Olivia Newton-John Cancer Research Institute, Victoria, Australia.|School of Cancer Medicine, La Trobe University, Victoria, Australia.|University of Melbourne, Victoria, Australia.
Thomas
T
John
D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008875:Middle Aged; D011379:Prognosis
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human