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

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