Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations

• Published in: Molecular cancer Vol. 18; no. 1; pp. 139 - 18
• Main Authors: Lin, Anqi, Wei, Ting, Meng, Hui, Luo, Peng, Zhang, Jian
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.09.2019; BioMed Central; BMC
• Subjects: Animals; Anti-PD-1/PD-L1 treatment; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Clinical trials; Decision making; EGFR mutations; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; Gene Expression Regulation, Neoplastic - drug effects; Gene mutations; Genetic aspects; Humans; Immune checkpoint inhibitors; Immunomodulation - drug effects; Immunotherapy; Inhibitors; Jian Zhang; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mutation; Neoplasm Metastasis; Neoplasm Staging; Non-small cell lung cancer; Non-small cell lung carcinoma; Patients; PD-1 protein; PD-L1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Review; Studies; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors; EGFR mutations; Tumor microenvironment; Anti-PD-1/PD-L1 treatment; Immunotherapy; Non-small cell lung cancer
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-019-1062-7

Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.