Immunotherapy in Lung Cancer: Current Landscape and Future Directions

• Published in: Frontiers in immunology Vol. 13; p. 823618
• Main Authors: Mamdani, Hirva, Matosevic, Sandro, Khalid, Ahmed Bilal, Durm, Gregory, Jalal, Shadia I.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 09.02.2022
• Subjects: Carcinoma, Non-Small-Cell Lung - drug therapy; cellular therapy; DNA repair; engineered immune cells; Humans; immune checkpoint inhibitors; Immunologic Factors - therapeutic use; Immunology; Immunotherapy; lung cancer; Lung Neoplasms - pathology; Small Cell Lung Carcinoma - drug therapy; lung cancer; immune checkpoint inhibitors; engineered immune cells; cellular therapy; DNA repair; immunotherapy
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.823618

Over the past decade, lung cancer treatment has undergone a major paradigm shift. A greater understanding of lung cancer biology has led to the development of many effective targeted therapies as well as of immunotherapy. Immune checkpoint inhibitors (ICIs) have shown tremendous benefit in the treatment of non-small cell lung cancer (NSCLC) and are now being used as first-line therapies in metastatic disease, consolidation therapy following chemoradiation in unresectable locally advanced disease, and adjuvant therapy following surgical resection and chemotherapy in resectable disease. Despite these benefits, predicting who will respond to ICIs has proven to be difficult and there remains a need to discover new predictive immunotherapy biomarkers. Furthermore, resistance to ICIs in lung cancer is frequent either because of a lack of response or disease progression after an initial response. The utility of ICIs in the treatment of small cell lung cancer (SCLC) remains limited to first-line treatment of extensive stage disease in combination with chemotherapy with modest impact on overall survival. It is thus important to explore and exploit additional targets to reap the full benefits of immunotherapy in the treatment of lung cancer. Here, we will summarize the current state of immunotherapy in lung cancer, discuss novel targets, and explore the intersection between DNA repair defects and immunotherapy.