Peripheral CD4⁺ T Cells Predict T Cell Immunity in Lung Tissues of Non-small Cell Lung Cancer Patients

Previous investigations showed that non-small cell lung cancer (NSCLC) patients with a high percentage of a peripheral CD4⁺ T cell subset were more likely to have severe immune-related adverse events (irAEs) due to anti-PD-1 therapy. The present study investigated the relationship between a peripheral CD4⁺ T cell subset and T cell immunity in the non-tumor lung tissues of patients with NSCLC to clarify the rationale of predictive biomarkers for anti-PD-1-related pneumonitis.

We analyzed the T cell profiles and functions in peripheral blood and non-tumor lung tissues surgically resected from patients with NSCLC.

In patients with NSCLC with a high percentage of the peripheral CD4⁺ T cell subset (CD45RA⁺CD25⁺CD4⁺ T cells), non-tumor lung tissues had a high percentage of PD-1⁺CD4⁺ T cells and a low percentage of PD-1⁺ effector regulatory T (Treg) cells. The percentage of PD-1⁺ effector Treg cells negatively correlated with IFNγ and TNFα production by CD4⁺ T cells in the lung tissues of patients with NSCLC.

Patients with NSCLC with a high percentage of the peripheral CD4⁺ T cell subset are at an increased risk of anti-PD-1-related pneumonitis, which activates PD-1⁺CD4⁺ T cells in the absence of the suppressive activity of effector Treg cells in lung tissues.