Abstract 1730P
Background
PDL1 expression has been correlated with response to immunotherapy among NSCLC patients. NSCLC with high PDL1 (≥50%) are more likely to respond to single agent anti-PD1 therapy comparing to those with low PDL1 (<50%). Hence, there might be biological differences between those two groups. We aimed to investigate the presence of differences between them in terms of pre-treatment TCR repertoire and genomic HLA-I.
Methods
We prospectively collected baseline blood from 90 NSCLC patients; 50 with high PDL1 and 40 with low PDL1. High quality DNA was extracted. TCR sequencing and high-resolution HLA typing was performed. TCR diversity and TCR gene usage was compared between both groups using a Mann-Whitney U test. HLA-I homozygosity at one or more loci versus maximal heterozygosity and HLA-A and -B supertypes were compared between the two groups using Fisher’s exact test to calculate relative risk. All analysis was conducted using GraphPad Prism version 9.3.1.
Results
Of the 90 patients, 84 had successful TCR sequencing (47 high and 37 low PDL1). Patients with high PDL1 are more likely to have higher TCR evenness (P=0.013) and lower clonality (P=0.008) compared to those with low or no PDL1. Moreover, certain TCR-genes are found more frequent among patients with high PDL1 like: TRBV3-1 (P=0.012), TRBV5-3 (P=0.029), TRBV9 (P=0.029), TRBV18 (P=0.019). Other TCR genes usage are found less frequent like: TRBV6-2 (P=0.040), TRBJ1-5 (P=0.032) and TRBJ2-7 (P=0.049). HLA typing was available for the 90 patients. No statistically significant result was found among both groups in terms of homozygosity versus heterozygosity. However, patients with high PDL1 are less likely to express HLA-A24 (RR=0.47, 95% CI 0.19-0.94, P=0.027) and more likely to express HLA-A03 (RR=1.87, 95% CI 1.24-2.98, P=0.002) on their cell surfaces.
Conclusions
Here we report that high PDL1 NSCLC are associated with distinct pre-treatment TCR repertoire and HLA-I supertypes comparing to low PDL1. Mechanistic studies are required to understand the biology of different types of NSCLC and hence have positive influence on treatment personalisation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Afaf Abed and Elin Gray.
Funding
Lung Foundation Australia.
Disclosure
All authors have declared no conflicts of interest.