Exploratory mass cytometry analysis reveals immunophenotypes of cancer treatment-related pneumonitis

Abstract

Anti-cancer treatments can result in various adverse effects, including infections due to immune suppression/dysregulation and drug-induced toxicity in the lung. One of the major opportunistic infections is Pneumocystis jirovecii pneumonia (PCP), which can cause severe respiratory complications and high mortality rates. Cytotoxic drugs and immune-checkpoint inhibitors (ICIs) can induce interstitial lung diseases (ILDs). Nonetheless, the differentiation of these diseases can be difficult, and the pathogenic mechanisms of such diseases are not yet fully understood. To better comprehend the immunophenotypes, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid from patients with PCP, cytotoxic drug-induced ILD (DI-ILD), and ICI-associated ILD (ICI-ILD) using two panels containing 64 markers. In PCP, we observed an expansion of the CD16+ T cell population, with the highest CD16+ T proportion in a fatal case. In ICI-ILD, we found an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.

Shared genetic etiology between hypothyroidism and complex diseases: a large-scale genome-wide cross-trait analysis

“…CD226, a member of the immunoglobulin superfamily, is a functional protein originally produced on natural killer and T cells [54]. A recent study has reported that CD226 expression in T cells from sarcoidosis [55]. Furthermore, it was proposed that CD4 T cells moving to the lungs via CXCR3 could be activated by CD226, potentially contributing to the pathogenesis of sarcoidosis.…”