Open Access

Anti‑PD‑1/PD‑L1 and anti‑CTLA‑4 associated checkpoint inhibitor pneumonitis in non‑small cell lung cancer: Occurrence, pathogenesis and risk factors (Review)

  • Authors:
    • Xiao Hu
    • Jin Ren
    • Qianfei Xue
    • Rumei Luan
    • Dongyan Ding
    • Jie Tan
    • Xin Su
    • Junling Yang
  • View Affiliations

  • Published online on: September 6, 2023     https://doi.org/10.3892/ijo.2023.5570
  • Article Number: 122
  • Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Immune checkpoint inhibitors (ICIs) play a significant anti‑tumor role in the management of non‑small cell lung cancer. The most broadly used ICIs are anti‑programmed death 1 (PD‑1), anti‑programmed cell death‑ligand 1, and anti‑cytotoxic T lymphocyte‑associated antigen‑4 monoclonal antibody. Compared with traditional chemotherapy, ICIs have the advantages of greater efficiency and more specific targeting. However, the resulting immune‑related adverse events limit the clinical application of ICIs, especially checkpoint inhibitor pneumonitis (CIP). CIP chiefly occurs within 6 months of administration of ICIs. Excessive activation and amplification of cytotoxic T lymphocytes, helper T cells, downregulation of regulatory T cells, and over‑secretion of pro‑inflammatory cytokines are the dominant mechanisms underlying the pathophysiology of CIP. The dysregulation of innate immune cells, such as an increase in inflammatory monocytes, dendritic cells, neutrophils and M1 polarization of macrophages, an increase in IL‑10 and IL‑35, and a decrease in eosinophils, may underlie CIP. Although contested, several factors may accelerate CIP, such as a history of previous respiratory disease, radiotherapy, chemotherapy, administration of epidermal growth factor receptor tyrosine kinase inhibitors, PD‑1 blockers, first‑line application of ICIs, and combined immunotherapy. Interestingly, first‑line ICIs plus chemotherapy may reduce CIP. Steroid hormones remain the primary treatment strategy against grade ≥2 CIP, although cytokine blockers are promising therapeutic agents. Herein, the current research on CIP occurrence, clinical and radiological characteristics, pathogenesis, risk factors, and management is summarized to further expand our understanding, clarify the prognosis, and guide treatment.
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November-2023
Volume 63 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hu X, Ren J, Xue Q, Luan R, Ding D, Tan J, Su X and Yang J: Anti‑PD‑1/PD‑L1 and anti‑CTLA‑4 associated checkpoint inhibitor pneumonitis in non‑small cell lung cancer: Occurrence, pathogenesis and risk factors (Review). Int J Oncol 63: 122, 2023.
APA
Hu, X., Ren, J., Xue, Q., Luan, R., Ding, D., Tan, J. ... Yang, J. (2023). Anti‑PD‑1/PD‑L1 and anti‑CTLA‑4 associated checkpoint inhibitor pneumonitis in non‑small cell lung cancer: Occurrence, pathogenesis and risk factors (Review). International Journal of Oncology, 63, 122. https://doi.org/10.3892/ijo.2023.5570
MLA
Hu, X., Ren, J., Xue, Q., Luan, R., Ding, D., Tan, J., Su, X., Yang, J."Anti‑PD‑1/PD‑L1 and anti‑CTLA‑4 associated checkpoint inhibitor pneumonitis in non‑small cell lung cancer: Occurrence, pathogenesis and risk factors (Review)". International Journal of Oncology 63.5 (2023): 122.
Chicago
Hu, X., Ren, J., Xue, Q., Luan, R., Ding, D., Tan, J., Su, X., Yang, J."Anti‑PD‑1/PD‑L1 and anti‑CTLA‑4 associated checkpoint inhibitor pneumonitis in non‑small cell lung cancer: Occurrence, pathogenesis and risk factors (Review)". International Journal of Oncology 63, no. 5 (2023): 122. https://doi.org/10.3892/ijo.2023.5570