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.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Our study was initially constrained by the availability of healthy individual controls but has been strengthened by incorporating single-cell RNA sequencing (scRNA-seq) data from healthy and COVID-19 subjects. Reviewer recommendations included the suggestion to explore more supportive data from the literature, as there are studies assessing immune markers in healthy bronchoalveolar lavage fluid (BALF). In response, we have integrated scRNA-seq data from healthy control BALF cells, finding that CD16 is expressed in a minority of T cells in healthy BALF. We have made corrections to typos and rearranged figures for logical flow. We have expanded on the discussion regarding the impact of immune checkpoint inhibitors (ICIs) on PD-1 expression, clarifying previous methodological limitations. Additionally, we have extended our analysis to correlate disease severity with various T-cell markers, noting a correlation with CCR7 expression. In summary, we have addressed reviewer comments and improved our manuscript by integrating additional control data, correcting errors, and expanding our analysis. We acknowledge the limitations of our study and suggest areas for future research. The study is commended for its potential significance in linking CD16+ T cells with disease severity and providing insights into the immunological underpinnings of cancer treatment-related pneumonitis.
