Dynamic cytokines signature predicts survival outcome from severe Immune-related hepatitis with PD-1/PD-L1 blockade in lung cancer.

Abstract

BACKGROUND:

Immune-related adverse events (irAEs), particularly immune-related hepatitis (IRH) is a potentially serious complication of immune checkpoint inhibitor (ICI) therapy. This retrospective cohort study investigated potential prognostic and predictive biomarkers for IRH.

METHOD:

This study included 37 patients with advanced lung cancer who received ICIs and were divided into two groups: ≥Grade 3 (G3)-IRH group (n = 17) and without irAE (no-irAE) group (n = 20). Blood samples collected at three different time points and pre-treatment tumor biopsy samples were analyzed using multi-omics assays.

RESULTS:

The IL-1B RNA expression was significantly increased (limma, fold = 1.94) in the ≥ G3-IRH group than the no-irAE group. Compared with no-irAE group, ≥G3-IRH group had higher monocyte and eosinophil infiltration and lower macrophage infiltration, particularly macrophage M2. Transcriptomics analyses of pre-treatment tumor samples revealed significant upregulation of various inflammation-related genes in the ≥ G3-IRH group (False discovery rate < 0.05). Moreover, various proinflammatory cytokines and chemokines were significantly lower in the plasma of the ≥ G3-IRH group than in the no-irAE group. Subgroup analyses of the ≥ G3-IRH group revealed that plasma IL-1A was significantly higher among those whose IRH resolved than those who had IRH-related death. Patients who died had a greater increase in immune score and Euclidean distance from the baseline to the seventh day of IRH onset, with a dramatic increase in Euclidean distance after immunosuppression, suggesting overstimulated immune status.

CONCLUSION:

Our study demonstrated the association between IL-1B overexpression and IRH susceptibility. Immune score and Euclidean distance of inflammatory cytokines may provide predictive value on the survival outcome from ≥ G3 IRH.

• Authors: Liang Zeng, Yuling Zhou, Qinqin Xu, Zhe Huang, Lianxi Song, Zhan Wang, Li Deng, Yongsheng Wu, Yanchao Liang, Zhentian Liu, Xuan Gao, Xin Yi, Qiongzhi He, Xuefeng Xia, Haiyan Yang, Xing Zhang, Huan Yan, Haoyue Qin, Shaoding Lin, Nong Yang, Yongchang Zhang
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 184 Pg. 107350 (10 2023) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 37659241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Immune Checkpoint Inhibitors
• B7-H1 Antigen
• Programmed Cell Death 1 Receptor

Topics

• Humans
• Lung Neoplasms (drug therapy)
• Cytokines
• Immune Checkpoint Inhibitors (adverse effects)
• B7-H1 Antigen (genetics)
• Programmed Cell Death 1 Receptor
• Retrospective Studies
• Hepatitis