Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: Focus on Nivolumab

Hazim Bukamur, MD; Heather Katz, DO; Mohamed Alsharedi, MD; Akram Alkrekshi, MD, PgDip, MRCP(UK); Yousef R. Shweihat, MD; Nancy J. Munn, MD


South Med J. 2020;113(11):600-605. 

In This Article

Abstract and Introduction


The development of checkpoint inhibitors has changed the treatment paradigm for cancer. Checkpoint inhibitors nivolumab, pembrolizumab, and cemiplimab target programmed death-1 (PD-1), whereas durvalumab, avelumab, and atezolizumab target PD-ligand 1. Ipilimumab targets cytotoxic T lymphocyte–associated antigen 4. Used as monotherapy or in combination, these inhibitors have shown remarkable efficacy in melanoma, lung cancer, urothelial cancer, and many other solid tumors, and indications are continuing to evolve. Checkpoint inhibitors are well tolerated when compared with traditional chemotherapy. The major adverse effect profiles are idiosyncratic immune-mediated toxicities resulting from the abnormal activation of autoreactive T cells, which can lead to inflammation in any organ system. The most commonly affected organs are bowel, lung, skin, and endocrine. Pulmonary toxicity is important to recognize, and it can be more challenging to diagnose in lung cancer patients, given the nature of the disease course and treatment. This review article focuses on all of the pulmonary adverse effects of a single PD-1 inhibitor (nivolumab) that have been described in the literature. These complications include dyspnea, pneumonitis, pleural effusion, pulmonary sarcoidosis, pulmonary tuberculosis, acute fibrinous organizing pneumonia, organizing pneumonia, eosinophilic pneumonia, adult respiratory distress syndrome, and lung cavitation. Clinicians must be aware of these toxicities and mindful when prescribing these medications in patients with known lung dysfunction due to chronic lung diseases or lung cancer.


Immune checkpoint inhibitors have become prevalent as first- and second-line treatments for many advanced and metastatic solid tumors (Table).[1] The principal mechanism for an immune checkpoint inhibitor is the removal of tumor-suppressing factor on the tumor cell rendering it exposed to the host immune system. This results in the enhancement of T cell activity, and destruction of the tumor cell follows. It starts with T cell receptors recognizing an antigen on the cell surface of tumor cells or host cells. What follows depends on the balance between co-stimulatory and co-inhibitory signals (immune checkpoints) on the interacting cells. When co-stimulatory signals overwhelm co-inhibitory signals, T cell activation occurs and vice versa. In the programmed death ligand-1(PD-L1)/PD-1 pathway, when PD-1 engages PD-L1, it attenuates T cell receptor and CD28 signaling through the recruitment of tyrosine phosphatases, resulting in T cell exhaustion.[2]