Patients with locally advanced non-small cell lung cancer (NSCLC), a heterogenous group encompassing stage IIIA-IIIC disease, often have surgically unresectable cancer and are managed with concurrent chemoradiation. Since the establishment of platinum-based chemoradiation as standard of care for unresectable locally advanced NSCLC, various strategies including escalating radiation dose, targeted therapies, antiangiogenic agents, and induction or consolidation chemotherapy have failed to show improvement in outcomes. However, recently, use of consolidation immunotherapy with durvalumab following concurrent chemoradiation therapy has been associated with improvement in survival and has led to a paradigm shift. In this review, we will summarize results from trials of immunotherapy in locally advanced NSCLC and comment on ongoing trials and potential future investigations.Blockade of the programmed cell death 1 immune inhibitory pathway has revolutionized the treatment of advanced non-small cell lung cancer and led to significant improvements in overall survival. In contrast, early-stage surgically resectable lung cancer has had few treatment advances in many years and continues to be associated with a high risk of relapse despite apparent curative resection. In this review, we discuss the many ongoing efforts to incorporate programmed cell death 1 pathway blockade into the treatment paradigm for surgically resectable lung cancer both as adjuvant and neoadjuvant therapy. We review the early-phase results from neoadjuvant clinical trials, the landscape of phase III trials that are ongoing, and look to the future of immune checkpoint blockade as a potential curative therapy for surgically resectable lung cancer.Immune-related adverse events (irAEs) are a common occurrence in patients treated with immune checkpoint inhibitors. Fortunately, the majority of irAEs are mild and easily managed with steroids. As the use of immune checkpoint inhibitors and other immune therapies continues to increase across indications, so too will the need for managing irAEs. Optimal care for irAEs should include surveillance and early detection, guideline-driven management of standard irAEs, multidisciplinary expert involvement in complicated or steroid-refractory cases, and concurrent research to define predictive biomarkers and delineate the populations, which can be safely treated and retreated with immune therapies. In this article, we describe the implementation of a 3-pronged strategy used at our institution consisting of an Immune Wellness Clinic to risk stratify and monitor at-risk patients, an Immuno-Oncology Treatment Monitoring Repository to support translational research, and an Immunotoxicity Tumor Board to manage severe or complicated adverse events.Immune checkpoint inhibitor (ICI) therapy is now in widespread clinical use for the treatment of lung cancer. Although patients with autoimmune disease and other comorbidities were excluded from initial clinical trials, emerging real-world experience suggests that these promising treatments may be administered safely to individuals with inactive low-risk autoimmune disease such as rheumatoid arthritis or psoriasis, mild to moderate renal and hepatic dysfunction, and certain chronic viral infections. Considerations for ICI in autoimmune disease populations include exacerbations of the underlying autoimmune disease, increased risk of ICI-induced immune-related adverse events, and potential for compromised efficacy if patients are receiving chronic immunosuppression. Immune checkpoint inhibitor use in higher-risk autoimmune conditions, such as myasthenia gravis or multiple sclerosis, requires careful evaluation on a case-by-case basis. Immune checkpoint inhibitor use in individuals with solid organ transplant carries a substantial risk of organ rejection. Ongoing research into the prediction of ICI efficacy and toxicity may help in patient selection, treatment, and monitoring.Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly defined by genetic alterations in oncogenic drivers. Targeted therapies have transformed the management of oncogene-driven lung cancers, with targeted agents now approved in the United States for 7 distinct molecular alterations. Nonetheless, acquired resistance remains an ongoing challenge, underscoring the need for alternative therapeutic approaches. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have emerged as important therapies in the management of advanced NSCLC, but the role of these agents in patients with oncogenic driver mutations remains unclear. Here, we focus on epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged NSCLC as paradigms to explore the role of immune checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview of the clinical data examining programmed death ligand 1 (PD-L1) inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor combinations, as well as combinations of PD-(L)1 inhibitors and chemotherapy.Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm for advanced non-small cell lung cancer (NSCLC). Although certain patients achieve significant, long-lasting responses from checkpoint blockade, the majority of patients with NSCLC do not and may be unnecessarily exposed to inadequate therapies and immune-related toxicities.  https://www.selleckchem.com/products/cc-930.html  Therefore, there is a critical need to identify biomarkers predictive of immunotherapy response. While tumor and immune cell expression of programmed death ligand-1 and, more recently, tumor mutational burden are used in clinical practice and may correlate with immunotherapy response in selected circumstances, neither consistently predicts an individual patient's likelihood of clinical benefit from ICI therapy. More recently, innovative approaches such as blood-based assays and combination biomarker strategies are under active investigation. This review will focus on the current role and challenges of programmed death ligand-1 and tumor mutational burden as predictive biomarkers for immunotherapy response in advanced NSCLC and explore promising novel biomarker strategies.