EGFR Inhibition Strongly Modulates the Tumour Immune Microenvironment in EGFR-Driven Non-Small-Cell Lung Cancer.

Autor:	Selenz C; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Compes A; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Mildred Scheel School of Oncology Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Nill M; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Borchmann S; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Odenthal M; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Florin A; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Brägelmann J; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Mildred Scheel School of Oncology Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Büttner R; Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Meder L; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Mildred Scheel School of Oncology Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany., Ullrich RT; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.; Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
Jazyk:	angličtina
Zdroj:	Cancers [Cancers (Basel)] 2022 Aug 16; Vol. 14 (16). Date of Electronic Publication: 2022 Aug 16.
DOI:	10.3390/cancers14163943
Abstrakt:	EGFR-driven non-small-cell lung cancer (NSCLC) patients are currently treated with TKIs targeting EGFR, such as erlotinib or osimertinib. Despite a promising initial response to TKI treatment, most patients gain resistance to oncogene-targeted therapy, and tumours progress. With the development of inhibitors against immune checkpoints, such as PD-1, that mediate an immunosuppressive microenvironment, immunotherapy approaches attempt to restore a proinflammatory immune response in tumours. However, this strategy has shown only limited benefits in EGFR-driven NSCLC. Approaches combining EGFR inhibition with immunotherapy to stimulate the immune response and overcome resistance to therapy have been limited due to insufficient understanding about the effect of EGFR-targeting treatment on the immune cells in the TME. Here, we investigate the impact of EGFR inhibition by erlotinib on the TME and its effect on the antitumour response of the immune cell infiltrate. For this purpose, we used a transgenic conditional mouse model to study the immunological profile in EGFR-driven NSCLC tumours. We found that EGFR inhibition mediated a higher infiltration of immune cells and increased local proliferation of T-cells in the tumours. Moreover, inhibiting EGFR signalling led to increased activation of immune cells in the TME. Most strikingly, combined simultaneous blockade of EGFR and anti-PD-1 (aPD-1) enhanced tumour treatment response in a transgenic mouse model of EGFR-driven NSCLC. Thus, our findings show that EGFR inhibition promotes an active and proinflammatory immune cell infiltrate in the TME while improving response to immune checkpoint inhibitors in EGFR-driven NSCLC.
Databáze:	MEDLINE
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