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ORAL 25 - Biology and Other Issues in SCLC (ID 125)
- Event: WCLC 2015
- Type: Oral Session
- Track: Small Cell Lung Cancer
- Presentations: 1
ORAL25.06 - Association of Expression of PD-L1 with the Tumor Immune Microenvironment in Small Cell Lung Cancer (ID 859)
10:45 - 12:15 | Author(s): D. Chan
Small cell lung cancer (SCLC) accounts for 15% of all lung cancers and has been under-studied relative to novel therapies. Therapeutic antibodies to immune checkpoints are showing promising clinical results. Programmed death-ligand 1 (PD-L1), which can be expressed on many cancer and immune cells, plays an important role in blocking the cancer immunity cycle by binding programmed death-ligand 1 receptor (PD-1), which is a negative regulator of T-lymphocyte activation. Since knowledge about PD-L1 expression in SCLC is limited, we aimed to characterize PD-L1 expression in a cohort of 98 SCLC patients.
PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC, SP142, Spring Bioscience) and mRNA in situ hybridization (ISH) in primary tumor tissue microarrays obtained from 98 SCLC patients. Membranous staining of PD-L1 protein and mRNA expression on tumor cells and protein expression on tumor-infiltrating immune cells (TIICs) were scored separately using semi-quantitative scores (H-score 0-300 and RNA score 0-4). An H-score ≥ 5 and an RNA score > 2 were defined as the cutoffs for PD-L1 protein and RNA expression positivity. The degree of TIICs was semi-quantitatively scored on hematoxylin and eosin-stained TMA slides as having “0” (no), “1” (mild), “2” (moderate), or “3” (marked) infiltration. The data was analyzed using the Fisher’s exact test, Spearman correlation, two-sample t-test, log-rank test and Kaplan- Meier survival analysis with significance level assumed to be 0.05.
3.16% of cases (3/95) were positive for PD-L1 protein expression in tumor cells, and 30.21% were positive for PD-L1 in TIICs (29/96, p<0.0001). PD-L1 mRNA expression was positive in 15.46% of the tumor cells (15/97). PD-L1 protein and mRNA expression on tumor cells demonstrated a positive correlation (p<0.0001, r=0.431). PD-L1 mRNA expression on tumor cells positively correlated with PD-L1 protein expression on TIICs (p<0.0001, r=0.354). The degree of TIICs positively correlated with both PD-L1 protein expression in tumor cells (p=0.011, r=0.264) and PD-L1 mRNA expression in tumor cells (p<0.0001, r=0.405). The degree of TIICs positively correlated with PD-L1 protein expression in TIICs (p<0.0001, r=0.625). The only significant association observed between PD-L1 expression with clinical characteristics or prognosis of the 78 SCLC patients with clinical data, was between age of patients and PD-L1 protein (p<0.0001) and mRNA expression (p=0.0006) on tumor cells.
A subset of SCLCs is characterized by positive PD-L1 protein and/or mRNA expression in tumor cells and TIICs. PD-L1 mRNA expression was more frequently positive than PD-L1 protein expression in the tumor cells. PD-L1 protein expression was expressed more in TIICs than tumor cells. Higher PD-L1 protein and mRNA expression correlated with more infiltration of TIICs. PD-L1 expression represents the immune response in SCLC. The microenvironment may play a major role on the PD-1/PD-L1 pathway of SCLC. SCLC Patients with PD-L1 expression may respond to anti-PD-L1 treatment.
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