Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.

Area of Science:

• Immunology
• Oncology
• Pulmonology

Background:

• Immune checkpoint inhibitors (ICIs) can cause pneumonitis in cancer patients.
• Understanding risk factors for ICI-related pneumonitis in non-small-cell lung cancer (NSCLC) is crucial.

Purpose of the Study:

• Investigate the role of autoantibodies and autoreactive T cells against surfactant proteins in ICI-related pneumonitis.
• Identify potential biomarkers for predicting and diagnosing pneumonitis during ICI therapy.

Main Methods:

• Analyzed serum autoantibodies and T cells in NSCLC patients before and during ICI treatment.
• Utilized proteomics, T-cell stimulation assays, and single-cell RNA sequencing.
• Validated findings in separate NSCLC and melanoma cohorts.

Main Results:

• Higher pretreatment immunoglobulin G autoantibodies targeting surfactant protein-B (SP-B) were found in patients who developed pneumonitis.
• Patients with pneumonitis showed increased CD4+ IFN-γ-positive SP-B-specific T cells and proinflammatory serum profiles.
• Expanding T-cell clonotypes recognizing SP-B were observed during pneumonitis onset.

Conclusions:

• Co-occurrence of SP-B autoantibodies and CD4+ T cells is associated with ICI-related pneumonitis.
• Pretreatment antibody levels may predict pneumonitis risk.
• On-treatment antibody levels could aid in diagnosis.