An increase in peripheral blood CD86-positive plasmacytoid dendritic cells is associated with immune-related adverse events after immune checkpoint inhibitor therapy in patients with non-small cell lung cancer

Background: The occurrence of immune-related adverse events (irAEs) after immune checkpoint inhibitors (ICIs) is unpredictable. Peripheral blood mononuclear cell (PBMC) profiles, representing host immune status, have potential for predicting irAEs. Methods: PBMC subsets were measured using multicolor flow cytometry before and at weeks 2 and 8 after the initiation of ICIs in patients with non-small cell lung cancer. Results: Sixteen evaluable patients were eligible for the analysis. The following irAEs occurred in 6 (37.5%) patients: diarrhea (n = 2), diarrhea and rash (n = 1), pneumonitis (n = 1), pituitary dysfunction (n = 1), and cholangitis (n = 1). Patients with irAEs demonstrated higher levels of CD86+plasmacytoid dendritic cells (pDCs) at baseline and weeks 2 and 8 after the ICIs than patients without irAEs (p = 0.005, 0.038, and 0.050, respectively). In patients with irAEs, the levels of CD86+pDCs decreased at weeks 2 and 8 compared with baseline (p =0 .034 and 0.025, respectively) but did not change in patients without irAEs. Other PBMC subsets had no significant associations with irAEs. Higher levels of natural killer (NK) cells were significantly associated with overall objective response (p = 0.024). Conclusions: Higher levels of CD86+pDCs at baseline and the reduction at 2 and 8 weeks after the ICIs were associated with the occurrence of irAEs. Higher levels of NK cells were associated with therapeutic efficacy. Measurements of PBMCs may be useful for predicting the efficacy and safety of ICIs.