IL-17C-mediated innate inflammation decreases the response to PD-1 blockade in a model of Kras-driven lung cancer.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Immunity, Innate*; Carcinoma, Non-Small-Cell Lung/*drug therapy ; Interleukin-17/*physiology ; Lung Neoplasms/*drug therapy ; Neoplasm Proteins/*antagonists & inhibitors ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Proto-Oncogene Proteins p21(ras)/*physiology; Animals ; B7-H1 Antigen/biosynthesis ; B7-H1 Antigen/genetics ; CD8-Positive T-Lymphocytes/immunology ; Carcinoma, Non-Small-Cell Lung/etiology ; Carcinoma, Non-Small-Cell Lung/immunology ; Cell Line, Tumor ; Cytokines/physiology ; Female ; Genes, ras ; Humans ; Interleukin-17/deficiency ; Interleukin-17/genetics ; Interleukin-17/pharmacology ; Lung Neoplasms/etiology ; Lung Neoplasms/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Molecular Targeted Therapy ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Neutrophils/physiology ; Programmed Cell Death 1 Receptor/biosynthesis ; Programmed Cell Death 1 Receptor/genetics ; Pulmonary Disease, Chronic Obstructive/complications ; Pulmonary Disease, Chronic Obstructive/immunology ; Recombinant Proteins/pharmacology ; Tumor Microenvironment

Chronic obstructive pulmonary disease (COPD) is associated with neutrophilic lung inflammation and CD8 T cell exhaustion and is an important risk factor for the development of non-small cell lung cancer (NSCLC). The clinical response to programmed cell death-1 (PD-1) blockade in NSCLC patients is variable and likely affected by a coexisting COPD. The pro-inflammatory cytokine interleukin-17C (IL-17C) promotes lung inflammation and is present in human lung tumors. Here, we used a Kras-driven lung cancer model to examine the function of IL-17C in inflammation-promoted tumor growth. Genetic ablation of Il-17c resulted in a decreased recruitment of inflammatory cells into the tumor microenvironment, a decreased expression of tumor-promoting cytokines (e.g. interleukin-6 (IL-6)), and a reduced tumor proliferation in the presence of Haemophilus influenzae- (NTHi) induced COPD-like lung inflammation. Chronic COPD-like inflammation was associated with the expression of PD-1 in CD8 lymphocytes and the membrane expression of the programmed death ligand (PD-L1) independent of IL-17C. Tumor growth was decreased in Il-17c deficient mice but not in wildtype mice after anti-PD-1 treatment. Our results suggest that strategies targeting innate immune mechanisms, such as blocking of IL-17C, may improve the response to anti-PD-1 treatment in lung cancer patients.

JCI Insight. 2016 Jun 16;1(9):e87415. (PMID: 27699275)
J Thorac Oncol. 2017 Aug;12(8):1268-1279. (PMID: 28483607)
Am J Physiol Lung Cell Mol Physiol. 2016 Nov 1;311(5):L1015-L1022. (PMID: 27694471)
Nat Rev Immunol. 2009 Aug;9(8):556-67. (PMID: 19575028)
Trends Immunol. 2017 May;38(5):310-322. (PMID: 28254169)
Respiration. 2011;81(4):265-84. (PMID: 21430413)
Cancer Res. 2005 Apr 15;65(8):3044-8. (PMID: 15833831)
Nat Rev Immunol. 2018 May;18(5):309-324. (PMID: 29379212)
Nature. 2015 Jan 22;517(7535):489-92. (PMID: 25363767)
Nat Immunol. 2011 Oct 12;12(12):1159-66. (PMID: 21993848)
Chest. 2012 May;141(5):1216-1223. (PMID: 22016483)
Nat Commun. 2017 Feb 01;8:14381. (PMID: 28146145)
Eur Respir J. 2010 Jun;35(6):1209-15. (PMID: 20513910)
Am J Physiol Lung Cell Mol Physiol. 2015 Sep 15;309(6):L605-13. (PMID: 26209273)
Cancer Cell. 2015 Apr 13;27(4):450-61. (PMID: 25858804)
Oncogene. 2017 Jul 20;36(29):4182-4190. (PMID: 28346430)
Science. 2015 Apr 3;348(6230):124-8. (PMID: 25765070)
Cancer Res. 2016 Mar 1;76(5):999-1008. (PMID: 26833127)
J Immunol. 2017 Jan 15;198(2):669-680. (PMID: 27956525)
Oncogene. 2014 May 22;33(21):2709-16. (PMID: 23812430)
Am J Respir Crit Care Med. 2018 Sep 15;198(6):777-787. (PMID: 29617574)
Am J Respir Crit Care Med. 2018 Oct 1;198(7):928-940. (PMID: 29518341)
Cancer Res. 2016 Jun 1;76(11):3189-99. (PMID: 27197187)
Gut. 2018 Feb;67(2):320-332. (PMID: 27797936)
Nat Commun. 2018 Nov 30;9(1):5099. (PMID: 30504842)
Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5664-9. (PMID: 24706787)
Cell Mol Immunol. 2016 Jul;13(4):474-83. (PMID: 26166766)
J Allergy Clin Immunol. 2016 Jul;138(1):16-27. (PMID: 27373322)
Nature. 2001 Apr 26;410(6832):1111-6. (PMID: 11323676)
Cancer Res. 2018 Sep 1;78(17):5011-5022. (PMID: 29967259)
Am J Pathol. 2017 May;187(5):973-979. (PMID: 28279655)
J Immunol. 2013 Mar 1;190(5):2252-62. (PMID: 23359500)
Cancer Cell. 2010 Jan 19;17(1):89-97. (PMID: 20129250)
J Immunol. 2019 Jan 1;202(1):160-170. (PMID: 30504421)
Innate Immun. 2016 Nov;22(8):620-625. (PMID: 27634821)
J Leukoc Biol. 2013 Oct;94(4):585-94. (PMID: 23543767)
J Immunol. 2002 Jul 1;169(1):443-53. (PMID: 12077275)
Am J Respir Cell Mol Biol. 2009 Apr;40(4):443-53. (PMID: 18927348)
Am J Respir Cell Mol Biol. 2014 Jan;50(1):30-9. (PMID: 23944933)
Nucleic Acids Res. 2001 May 1;29(9):e45. (PMID: 11328886)
J Thorac Dis. 2017 May;9(5):E468-E469. (PMID: 28616311)
Am J Respir Cell Mol Biol. 2008 Jun;38(6):629-38. (PMID: 18096867)
Oncogene. 2014 Mar 6;33(10):1239-48. (PMID: 23563178)
Immunity. 2011 Oct 28;35(4):611-21. (PMID: 21982598)
Am J Respir Cell Mol Biol. 2013 May;48(5):531-9. (PMID: 23328639)
Am J Respir Cell Mol Biol. 2013 Apr;48(4):415-21. (PMID: 23221046)
Am J Respir Crit Care Med. 2018 Jul 1;198(1):24-38. (PMID: 29756991)
Cancer Res. 2015 Aug 15;75(16):3209-15. (PMID: 26122841)
Eur Respir J. 2009 Aug;34(2):380-6. (PMID: 19196816)
Cancer Discov. 2014 Apr;4(4):452-65. (PMID: 24444711)
Nat Immunol. 2011 Oct 12;12(12):1151-8. (PMID: 21993849)
Am J Respir Crit Care Med. 2016 Mar 15;193(6):642-51. (PMID: 26517304)
Cancer Discov. 2013 Dec;3(12):1355-63. (PMID: 24078774)
Am J Respir Crit Care Med. 2018 Feb 1;197(3):325-336. (PMID: 28934595)
Mol Cancer. 2013 Dec 09;12(1):154. (PMID: 24321240)
Cancer Res. 2016 Feb 15;76(4):866-76. (PMID: 26744530)

0 (B7-H1 Antigen)
0 (Cd274 protein, mouse)
0 (Cytokines)
0 (IL17C protein, human)
0 (Il17c protein, mouse)
0 (Interleukin-17)
0 (Neoplasm Proteins)
0 (Pdcd1 protein, mouse)
0 (Programmed Cell Death 1 Receptor)
0 (Recombinant Proteins)
EC 3.6.5.2 (Hras protein, mouse)
EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))

Date Created: 20190719 Date Completed: 20201026 Latest Revision: 20210110

20221213

PMC6637115

10.1038/s41598-019-46759-8

31316109