Abstract

Background: Checkpoint inhibitor pneumonitis (CIP) is a serious adverse reaction after immunotherapy and the immune dysregulation is considered the main cause. But the disordered types of immune cells were inconsistent in different reports. And there are no studies to analyze the clinical characteristics of different immune cells in CIP, and no in vivo model for CIP induced by PD-1 inhibitors.

Methods: CIP patients were included from 4 study centers to analyze the clinical features based on immune cell types. PD-1 humanized mice used to explore the vivo models of CIP by histopathology.

Result: Thirty-nine CIP patients were enrolled. Based on the type of percentage-increased immune cells in peripheral blood, 5 different subtypes of CIP could be classified, including monocytic type(43.6%), neutrophilic type(25.6%), lymphocytic type(15.4%), mixed type(12.8%) and eosinophilic type(2.6%).The main pneumonia grades of these subtypes were shown in Figure 1.Imaging features of patients with neutrophilic type were Crytogenic organizing pneumonia-like mainly, while the lymphocytic type tended more to be Ground glass opacities. And the mortality rate of neutrophilic type were the worst. Besides, in the vivo models induced by anti-PD1, the inflammation could be observed in each organ (Figure 2), and the incidence of CIP was 40%.

Conclusion: Checkpoint inhibitor pneumonitis can be classified into 5 inflammatory subtypes, and there are differences in CIP grade, imaging features and prognosis among subtypes. The vivo models of CIP could be induced by anti-PD1.