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

Anticancer 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.