PMC9335486_01
(A) On April 29, 2020, chest computed tomography (CT) before chemotherapy showed mild ground glass opacity in the lower lobe of the right lung. (B) On December 1, 2020, after 6 months of tislelizumab treatment, chest CT showed diffuse ground glass and solid opacity in both lungs, more severe in both lower lungs. (C) On December 24, 2020, after 3 weeks of prednisone treatment, chest CT showed pulmonary infiltration had improved. (D) pulmonary infiltration continued to improve on Feb 19, 2021. (E) Multiple subpleural ground glass lesions recurred in both lungs on May 2, 2021 (The patient received 10 mg prednisone). (F) The patient responded to azathioprine (150 mg per day) on November 19, 2021.
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The patient was a non-smoker with no history of pulmonary disease, but chest computed tomography (CT) before chemotherapy showed mild ground glass opacity in the lower lobe of the right lung ( Figure 1A ). C, no cough, or dyspnea ( Figure 2 ). Chest computed tomography (CT) showed multiple consolidations and ground-glass lesions in both lungs ( Figure 1B ). Chest CT showed that the ground glass and consolidation of both lungs improved significantly over 3 weeks ( Figure 1C ), and prednisone was gradually reduced. Pulmonary infiltration continued to improve on Feb 19, 2021 ( Figure 1D ). Multiple subpleural ground glass lesions recurred in both lungs on May 2, 2021 (the patient received 10 mg prednisone at that time) ( Figure 1E ). There was no sign of CIP or bladder cancer recurrence until last follow up in Nov 11, 2021 ( Figure 1F ).
Timeline scheme of major clinical event of the patient since treatment.
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C, no cough, or dyspnea ( Figure 2 ). Chest computed tomography (CT) showed multiple consolidations and ground-glass lesions in both lungs ( Figure 1B ).
Lung tissue histopathology showed organizing pneumonia with mildly thickened alveolar septa, fibroblastic proliferation filling airspaces, and moderate lymphocytic infiltrate. (A) HE, low power field. (B) HE, high power field. (Hematoxylin-eosin, HE).
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He was transferred to the respiratory department for transbronchial cryobiopsy, and bronchoalveolar lavage fluid classification showed predominantly lymphatic cells (38%), the histopathology showed organizing pneumonia ( Figure 3 ).
The microenvironment in patients with immune checkpoint inhibitor-related pneumonitis. (A-C) Imaging mass cytometry (IMC) imaging of formalin-fixed paraffin-embedded lung tissue specimen. (D) Statistical t-distributed stochastic neighbor embedding (tSNE) plots were generated to divide the cell populations into 11 clusters according to phenotypic similarity. (E) Heat map analysis of the mean expression of analyzed markers from 11 identified clusters. The expression levels are indicated by heat colors. (F) Neighborhood analysis revealed cell-to-cell interactions between different clusters.
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The cells in clusters 1-8 represented immune cells ( Figure 4D ). We identified infiltrating immune cell types of CD14+ monocytes, CD16+ monocytes, CD4+ T cells, CD8+ T cells, and CD68+ macrophages in lung tissues ( Figure 4E ). Abundant T cells were present in the inflammatory region, which were mainly CD45RA-CD45RO+ CD4+ T cells (cluster 2) and CD45RA-CD45RO+ CD8+ T cells (cluster 3), indicating the infiltration of memory T cells in pneumonitis tissues ( Figure 4A ). CD68+ macrophages, CD14+ monocytes, and CD11c+CD16+DC cells. CD68+ macrophages expressed a high level of HLA-DR ( Figure 4B ), indicating the M1-like phenotype. CD11c+CD16+ monocytes were also positive for CD4 and HLR-DR, and the data suggested that the CD4+ DC subset was activated. In addition, using neighborhood analysis, we found a cell-cell contact between CD8+ T cells and CD11c+ CD16+ DC in the microenvironment, indicating the interaction of DC-T cells and activation of CD8+ T cells ( Figures 4C, F ).