Analysis of Peripheral T Cell Profiling and Plasma Proteomics in Advanced NSCLC Patients Treated With Atezolizumab

Abstract

We investigated immunologic biomarkers that predict outcomes of patients with previously treated metastatic non-small cell lung cancer who were enrolled in the J-TAIL study, a prospective, observational study of atezolizumab monotherapy. Of 262 patients participating in the J-TAIL exploratory study, peripheral blood mononuclear cells were obtained from 51 patients and analyzed by T-cell fractionation analysis using Helios mass cytometry and serum proteomics analysis. Following treatment with atezolizumab, an increase in programmed cell death-1 (PD-1)-expressing CD8 and CD4 T-cell populations was observed. A more pronounced increase in PD-1 expression was seen in T cells from patients whose progression-free survival (PFS) was 100 days or longer compared with those with shorter PFS. The proximity extension assay, which is highly sensitive multiplex analysis technology that combines antibody-based affinity assays with next-generation sequencing, showed a significant increase in FOXO1, possibly in response to precursor-exhausted T-cell population activation. Immune-related adverse events were associated with a high percentage of PD-1-positive cells on effector memory CD8 T cells, which was thought to be accompanied by extremely high CD8 T-cell activation. Further analysis distinguished poor prognosis populations with significant differences in CD62L_high Th7R and CXCR3⁺ component of Th7R (CXCR3⁺ Th7R) within the population with PFS < 50 days. Patients with low Th7R or CXCR3⁺ Th7R percentages prior to atezolizumab treatment had significantly poorer overall survival. These findings provide valuable insights regarding T-cell kinetics and biomarkers in atezolizumab therapy and may offer promising directions for future research.

Trial Registration: UMIN Clinical Trials Registry: UMIN000033133 and UMIN000035567; ClinicalTrials.gov: NCT03645330