Science subjournal: blocking EGFR to improve the efficacy of anti PD-1 drugs on EGFR mutant lung adenocarcinoma

February 5, 2020 / Biovalley BIOON / - -- lung cancer is one of the major causes of cancer-related deaths worldwide About 80% of lung cancer cases are classified as non-small cell lung cancer (NSCLC) Several carcinogenic driving genes have been reported in NSCLC, including epidermal growth factor receptor (EGFR) coding gene and anaplastic lymphoma kinase (ALK) coding gene People have successfully developed molecular targeted therapies for these driving gene changes, thus improving the prognosis of patients EGFR activated mutations were found in 50% of lung adenocarcinoma in East Asia, including Japan Although patients with EGFR mutations initially respond to EGFR tyrosine kinase inhibitors, these patients often subsequently develop resistance to this treatment Therefore, there is an urgent need for effective treatment strategies Recently, immunocheckpoint blocking strategies, including PD-1 mAb and PD-L1 mAb, have shown impressive antitumor effects in NSCLC, thus ushering in a new era of NSCLC treatment However, its efficacy is less than 50%, so it is necessary to develop methods to improve the efficacy The clinical efficacy of anti-PD-1 monoclonal antibody against cancer with carcinogenic driving gene mutation (usually with low burden of tumor mutation) varies from person to person, which suggests that each driving mutation has different contribution to immune response In a new study, researchers from Japan's National Cancer Center and Nagoya University and other research institutions studied the immunophenotypes in tumor microenvironment (TME) of EGFR mutated lung adenocarcinoma, In the case of lung adenocarcinoma with EGFR mutation, anti-PD-1 monoclonal antibody treatment is largely ineffective The relevant research results were published in the Journal of science immunology on January 31, 2020 The title of the paper is "blockade of EGFR improvements response to PD-1 blockade in EGFR mutated non – small cell lung cancer" Picture from science immunology, 2020, DOI: 10.1126/sciimmunologol.aav3937 However, the EGFR mutant lung adenocarcinoma has an uninflammatory immunosuppressive tumor microenvironment, whereas the CD4 + effector regulatory T cell, which is usually present in the inflammatory tumor microenvironment, shows a high level of infiltration there EGFR signal activated JNK (cjun N-terminal kinase) and cjun and reduced ifn-1 (IRF1): the former increased CCL22, thus recruiting CD4 + regulatory T cells; the latter decreased CXCL10 and CCL5, thus inducing CD8 + T cell infiltration As a clinically available EGFR inhibitor, erlotinib can reduce the CD4 + effect in tumor microenvironment and regulate T cell infiltration in mouse model of lung adenocarcinoma mutated by EGFR, and the combination of erlotinib and anti-PD-1 monoclonal antibody shows better antitumor effect than either of the two drugs alone These results suggest that EGFR inhibitors, when combined with anti-PD-1 monoclonal antibody, may improve the efficacy of immunotherapy in lung adenocarcinoma In view of the clinical use of anti-PD-1 monoclonal antibody and erlotinib, this preclinical proof of concept study should be the basis of the clinical study to explore whether erlotinib can enhance the response of EGFR mutant lung adenocarcinoma to anti-PD-1 monoclonal antibody (BIOON Com) reference: ERI Sugiyama et al Blockade of EGFR improvements response to PD-1 blockade in EGFR mutated non – small cell lung cancer Science immunology, 2020, DOI: 10.1126/scientific.aav3937