Pneumonitis Induced by Immune Checkpoint Inhibitors: From Clinical Data to Translational Investigation

Abstract

Immune checkpoint inhibitors (ICIs) have been applied to clinical practice and achieved significant therapeutic benefit in a variety of human malignancies. These drugs not only enhance the body's antitumor immune response but also produce side effects called immune-related adverse events (irAEs). Although checkpoint inhibitor pneumonitis (CIP) has a low clinical incidence, it is likely to cause the delay or termination of immunotherapy and treatment-related death in some severe cases. An increasing number of CIP cases have been reported since 2015, which are attributed to the augmentation of approvals and uses of ICIs, but a comprehensive understanding of CIP is still lacking. This review focuses on the epidemiology, clinical characteristics, treatment strategies, and underlying mechanisms of CIP to strengthen the recognition of pulmonary toxicity among clinicians and researchers.

Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC

“…24 A meta-analysis revealed that ICI-associated allgrade and grade 3 or greater pneumonitis occur in approximately 3% and less than 1% of patients, respectively, in advanced cancer clinical trials, with 0.2% of patients dying. 16 The incidence was higher in patients treated outside NSCLC clinical trials: 19% all grade and 12% grade 3 or greater. 25 Incidence of immune-related pneumonitis varied by agent (anti-CTLA-4 versus PD-1 or PD-L1 inhibitors), regimen (combination versus monotherapy), medical history, and baseline disease characteristics.…”

Peripheral blood interleukin 6, interleukin 10, and T lymphocyte levels are associated with checkpoint inhibitor induced pneumonitis: a case report

“…Checkpoint inhibitor-induced pneumonitis (CIP) is a serious and potentially life-threatening irAE that can occur in cancer patients treated with immunotherapy [3,4]. Diagnostic evaluation of CIP involves patient's history, physical exam, laboratory values, and imaging findings has been summarized extensively elsewhere [3,[5][6][7]. The underlying mechanisms of CIP are unknown but increased proinflammatory lymphocytes are known to be enriched in the lungs during CIP and peripheral increases in inflammatory biomarkers, including CRP and interleukin 6 (IL-6), have been observed in a variety of inflammatory lung conditions, including CIP [6].…”

“…Diagnostic evaluation of CIP involves patient's history, physical exam, laboratory values, and imaging findings has been summarized extensively elsewhere [3,[5][6][7]. The underlying mechanisms of CIP are unknown but increased proinflammatory lymphocytes are known to be enriched in the lungs during CIP and peripheral increases in inflammatory biomarkers, including CRP and interleukin 6 (IL-6), have been observed in a variety of inflammatory lung conditions, including CIP [6]. To decrease pulmonary inflammation, the management, and treatment of CIP is based on discontinuing of ICIs and giving immunosuppressive treatments such as corticosteroids and IL-6 blockade [7].…”

Pulmonary Toxicities Associated With the Use of Immune Checkpoint Inhibitors: An Update From the Immuno-Oncology Subgroup of the Neutropenia, Infection & Myelosuppression Study Group of the Multinational Association for Supportive Care in Cancer

“…The time from the administration of the first dose of an ICI to the occurrence of ICI-Pneumonitis varies widely from 1.9 to 24 months, with a median time of 2.8 months (Hassel et al, 2017;Wang et al, 2021). Earlier occurrences have been reported with combination therapies (median 2.7 vs. 4.6 months) and among patients with lung cancer (2.1 months) compared to melanoma (5.1 months) (Zhu et al, 2020).…”

“…Pneumonitis is the primary manifestation of lung irAEs. Pleural effusions, airway disease, and mediastinal lymphadenopathy associated with sarcoid-like reactions have also been described (Nishino et al, 2017a;Suresh et al, 2018b;Gkiozos et al, 2018;Rambhia et al, 2019;Mitropoulou et al, 2020;Naidoo et al, 2020;Nobashi et al, 2020;Shannon, 2020;Zhu et al, 2020). Most cases of ICIrelated lung injury are mild, but these events may be irreversible and fatal.…”