7P - A T-cell-derived circulating DNA as a biomarker for response to anti-PD(L)1 immunotherapy in advanced stage non-small cell lung cancer

Background

PD-L1 expression is a current predictive biomarker of anti-PD-(L)1 immunotherapy in advanced non-small cell lung cancer (NSCLC) but has many limitations as a stand-alone biomarker. Tumor infiltrating T-lymphocyte might be the source of T-cell-derived circulating DNA. We explored T-cirDNA as a potential biomarker of anti-PD (L)1 inhibitor and its correlation tumor-infiltrating lymphocytes (TILs).

Methods

The prospective cohort of 78 advanced NSCLC who received anti-PD-(L)1 immunotherapy as monotherapy or combination fashion. Pre-treatment plasma T-cirDNA target rearranged TCR-β CDR3 region were quantified using multiplex real-time PCR assay. FFPE Tissue from 40 patients were stained using CD8 (C8-144B-Dako) and FOXP3 (236A/E7- Abcam). We defined patients into undetectable, low (<1% ratio) and high (>1% ratio) T-cirDNA/cirDNA. Baseline clinicopathological characteristic and prognostic factors were integrated by cox-regression analysis. The correlation of T-cirDNA/cirDNA and CD8/FOXP3 TILs were explored.

Results

77% of participants had detectable T-cirDNA/cirDNA with a median of 0.02 [range 52.3] ngml^-1. At median follow-up of 15.5 months, multivariate analysis revealed undetectable T-cirDNA/cirDNA and available subsequent treatment shown overall survival (OS) with the HR of 0.203 [95% CI 0.053-0.781, p-value 0.02] and 0.188 [95% CI 0.051-0.689 p-value 0.01] respectively. High level of T-cirDNA/cirDNA also correlated with better treatment outcome with the HR of 0.211 [95%Cl 0.055-0.815, p-value 0.02]. High level of T-cirDNA/cirDNA correlated with presence of intra-tumoral CD8 TIL 58.3% higher than low and undetectable T-cirDNA/cirDNA, 28.6% and 33.3% (p-value 0.17 and 0.19) respectively.

Conclusions

T-cell-derived circulating DNA shown paradoxical prognostic effect to anti-PD(L)1 treatment. The correlation with intra-tumoral CD8 TIL was demonstrated.

Legal entity responsible for the study

The authors.

Funding

National Research Council of Thailand (Grant number 347/2564).

Disclosure

All authors have declared no conflicts of interest.