Unveiling the Immunophenotypes of Pneumonitis in Cancer Treatment Through Mass Cytometry Exploration

<bold>Background and Aims</bold> 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). The objective of this study was to identify biomarkers that can distinguish between these diseases and investigate their pathogenic mechanisms. <bold>Methods:</bold> An exploratory mass cytometry analysis was conducted to evaluate immune cell subsets in bronchoalveolar lavage fluid from patients with PCP (n=7), cytotoxic drug-induced ILD (DI-ILD) (n=9), and ICI-associated ILD (ICI-ILD) (n=9). Two panels were used in the analysis, containing 64 markers. <bold>Results:</bold> Expansion of the CD16+ T cell population was observed in PCP patients, with the highest proportion of CD16+ T cells observed in a fatal case. In ICI-ILD cases, there was an increase in CD57+ CD8+ T cells expressing immune checkpoints (TIGIT+ LAG3+ TIM-3+ PD-1+), FCRL5+ B cells, and CCR2+ CCR5+ CD14+ monocytes. <bold>Conclusion:</bold> These findings uncover the diverse immunophenotypes and possible pathomechanisms of cancer treatment-related pneumonitis.