Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib.
The central immune co-inhibitory programmed cell death receptor/ligand 1 (PD-1/PD-L1) pathway plays a key role in tumor immune evasion in non-small cell lung cancer (NSCLC). Soluble PD-1 (sPD-1) can be detected in the blood, and preclinical evidence suggests that sPD-1 blocks PD-1/-L1 interaction and improves anti-tumor immunity. The present study compares the concentration of sPD-1 in the serum of advanced NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation prior to erlotinib treatment and at the time of progression and correlates these results to patient outcome.



Blood samples from 38 patients with EGFR-mutated advanced NSCLC treated with erlotinib were analyzed for sPD-1 by sandwich ELISA. EGFR mutational status was assessed in circulating tumor DNA (ctDNA) and tumor biopsies.



sPD-1 could be detected in 21% of patients prior to erlotinib treatment, and at disease progression in 37% (p=0.015). An increase in sPD-1 during erlotinib therapy was found in 34%, a decrease in 8% and no change in 58% of patients. An increase in sPD-1 during treatment was associated with prolonged progression-free (adjusted HR 0.32, p=0.013) and overall survival (adjusted HR 0.33, p=0.006), but not associated with the emergence of EGFR T790M mutation in ctDNA at progression or any clinicopathological factors.



Patients with an increase in sPD-1 during erlotinib treatment have a more favorable outcome. Our results emphasize the vast clinical impact of the PD-1/PD-L1 axis, and support the existing preclinical evidence in the bioactive function of sPD-1.
Department of Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark. Electronic address: stesoe@rm.dk.
Steffen Filskov
SF
Sorensen
Department of Clinical Biochemistry, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
Christina
C
Demuth
Department of Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
Britta
B
Weber
Department of Clinical Biochemistry, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
Boe Sandahl
BS
Sorensen
Department of Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark.
Peter
P
Meldgaard
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D061026:Programmed Cell Death 1 Receptor / Q000097:blood*; D011799:Quinazolines / Q000627:therapeutic use*; D016019:Survival Analysis; D019139:Tumor Escape
D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D004273:DNA, Neoplasm; D061026:Programmed Cell Death 1 Receptor; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
EGFR mutation; Erlotinib; Non-small cell lung cancer; Soluble PD-1; Tumor microenvironment