PT - JOURNAL ARTICLE AU - Deborah Ayeni AU - Braden Miller AU - Alexandra Kuhlmann AU - Ping-Chih Ho AU - Camila Robles-Oteiza AU - Mmaserame Gaefele AU - Stellar Levy AU - Fernando J. de Miguel AU - Curtis Perry AU - Tianxia Guan AU - Gerald Krystal AU - William Lockwood AU - Daniel Zelterman AU - Robert Homer AU - Zongzhi Liu AU - Susan Kaech AU - Katerina Politi TI - Tumor regression mediated by oncogene withdrawal or erlotinib stimulates infiltration of inflammatory immune cells in EGFR mutant lung tumors AID - 10.1186/s40425-019-0643-8 DP - 2019 Dec 01 TA - Journal for ImmunoTherapy of Cancer PG - 172 VI - 7 IP - 1 4099 - http://jitc.bmj.com/content/7/1/172.short 4100 - http://jitc.bmj.com/content/7/1/172.full SO - J Immunother Cancer2019 Dec 01; 7 AB - Background Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) like erlotinib are effective for treating patients with EGFR mutant lung cancer; however, drug resistance inevitably emerges. Approaches to combine immunotherapies and targeted therapies to overcome or delay drug resistance have been hindered by limited knowledge of the effect of erlotinib on tumor-infiltrating immune cells.Methods Using mouse models, we studied the immunological profile of mutant EGFR-driven lung tumors before and after erlotinib treatment.Results We found that erlotinib triggered the recruitment of inflammatory T cells into the lungs and increased maturation of alveolar macrophages. Interestingly, this phenotype could be recapitulated by tumor regression mediated by deprivation of the EGFR oncogene indicating that tumor regression alone was sufficient for these immunostimulatory effects. We also found that further efforts to boost the function and abundance of inflammatory cells, by combining erlotinib treatment with anti-PD-1 and/or a CD40 agonist, did not improve survival in an EGFR-driven mouse model.Conclusions Our findings lay the foundation for understanding the effects of TKIs on the tumor microenvironment and highlight the importance of investigating targeted and immuno-therapy combination strategies to treat EGFR mutant lung cancer.Abbreviations:AMAlveolar MacrophageEGFREpidermal Growth Factor ReceptorGzmbGranzyme BMRIMagnetic Resonance ImagingTH1T helper type 1TKITyrosine kinase inhibitorTMETumor microenvironmentTregRegulatory T cell