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Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR -mutated non-small cell lung cancer.
- Source :
-
Science immunology [Sci Immunol] 2020 Jan 31; Vol. 5 (43). - Publication Year :
- 2020
-
Abstract
- The clinical efficacy of anti-PD-1 (programmed cell death-1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions of each driver mutation to immune responses. Here, we investigated the immunological phenotypes in the tumor microenvironment (TME) of epidermal growth factor receptor ( EGFR )-mutated lung adenocarcinomas, for which anti-PD-1 mAb is largely ineffective. Whereas EGFR -mutated lung adenocarcinomas had a noninflamed TME, CD4 <superscript>+</superscript> effector regulatory T cells, which are generally present in the inflamed TME, showed high infiltration. The EGFR signal activated cJun/cJun N-terminal kinase and reduced interferon regulatory factor-1; the former increased CCL22, which recruits CD4 <superscript>+</superscript> regulatory T cells, and the latter decreased CXCL10 and CCL5, which induce CD8 <superscript>+</superscript> T cell infiltration. The EGFR inhibitor erlotinib decreased CD4 <superscript>+</superscript> effector regulatory T cells infiltration in the TME and in combination with anti-PD-1 mAb showed better antitumor effects than either treatment alone. Our results suggest that EGFR inhibitors when used in conjunction with anti-PD-1 mAb could increase the efficacy of immunotherapy in lung adenocarcinomas.<br /> (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Carcinoma, Non-Small-Cell Lung genetics
Cell Line, Tumor
Drug Synergism
ErbB Receptors antagonists & inhibitors
ErbB Receptors genetics
Humans
Lung Neoplasms genetics
Mutation
Antibodies, Monoclonal therapeutic use
Antineoplastic Agents therapeutic use
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Programmed Cell Death 1 Receptor antagonists & inhibitors
Protein Kinase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2470-9468
- Volume :
- 5
- Issue :
- 43
- Database :
- MEDLINE
- Journal :
- Science immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32005679
- Full Text :
- https://doi.org/10.1126/sciimmunol.aav3937