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Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non-small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.

Original publication




Journal article


Clinical cancer research : an official journal of the American Association for Cancer Research

Publication Date





4592 - 4602


Department of Medicine (Section of Medical Oncology), Yale University School of Medicine, New Haven, Connecticut.


Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Immunologic Factors, Immunotherapy, Clinical Trials as Topic, Antineoplastic Agents, Immunological, B7-H1 Antigen