CD4 and Interstitial pneumonitis: Although pre-clinical studies suggest that treatment of EGFR-TKIs would inflaming immune microenvironment via improve T cell infiltration and decrease the infiltration of CD4+ regulatory T cells (6, 20, 21), further clinical trials showed that combination of EGFR-TKIs and anti-PD-1 therapy lead to an unacceptable occurrence rate of adverse events, especially interstitial pneumonitis (10, 22).