The SP142 PD-L1 IHC assay for atezolizumab (atezo) reflects pre-existing immune status in NSCLC and correlates with PD-L1 mRNA

Abstract

Background: PD-L1 expression as measured by the SP142 PD-L1 IHC assay is associated with improved efficacy with atezo in patients with NSCLC, including overall survival. In capturing PD-L1 on both tumor cells (TC) and tumor-infiltrating immune cells (IC), this assay is able to determine preexisting immune status, underscoring the predictive value of PD-L1 IHC. In this study, we further investigated intratumoral immune infiltration status by measuring T effector (Teff ) gene signature and correlated PD-L1 mRNA expression with SP142 PD-L1 IHC. Methods: Using the SP142 IHC assay, procured samples from NSCLC tumors were scored according to the percent of TC expressing PD-L1 (TC0 < 1%; TC1 ≥ 1% and < 5%; TC2 ≥ 5% and < 50%; TC3 ≥ 50%). IC were scored as percentage of tumor area (IC0 < 1%; IC1 ≥ 1% and < 5%; IC2 ≥ 5% and < 10%; IC3 ≥ 10%). Four mutually exclusive groups increasing in PD-L1 expression (TC0 and IC0, TC1 or IC1, TC2 or IC2, TC3 or IC3) were designated. mRNA levels for PD-L1 and Teff signature were measured in the same NSCLC specimens using the Fluidigm platform and correlated with each of the PD-L1 IHC sub-groups. Results: In 86 NSCLC specimens, mRNA levels for PD-L1 increased incrementally with higher PD-L1 IHC status, from 0 median expression for TC0 and IC0 tumors to 3.14 median expression for TC3 or IC3 tumors. A similar trend was seen for the Teff signature, with values increasing from 0 to 1.65 median expression with increasing IHC cutoffs (Table). Conclusions: Results from the SP142 PD-L1 IHC assay associates with PD-L1 and Teff mRNA transcripts, reflecting pre-existing immunity associated with adaptive PD-L1 expression on IC as well as intrinsic PD-L1 expression on TC in NSCLC, thus providing an independent orthogonal correlation of IHC to gene expression. The value of mRNA gene expression as a predictive marker of efficacy for atezo in NSCLC is being studied in ongoing randomized trials of atezo. Median expressions are log scale expression (-ΔCT) relative to the median of TC0 and IC0 group. Larger values indicate higher expression. (Table Presented).