IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer

Ran You; Francesco J. DeMayo; Jian Liu; Sung Nam Cho; Bryan M. Burt; Chad J. Creighton; Roberto F. Casal; Donald R. Lazarus; Wen Lu; Hui Ying Tung; Xiaoyi Yuan; Andrea Hill-McAlester; Myunghoo Kim; Sarah Perusich; Loraine Cornwel; Daniel Rosen; Li Zhen Song; Silke Paust; Gretchen Diehl; David Corry; Farrah Kheradmand

doi:10.1158/2326-6066.CIR-17-0554

IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer

Ran You, Francesco J. DeMayo, Jian Liu, Sung Nam Cho, Bryan M. Burt, Chad J. Creighton, Roberto F. Casal, Donald R. Lazarus, Wen Lu, Hui Ying Tung, Xiaoyi Yuan, Andrea Hill-McAlester, Myunghoo Kim, Sarah Perusich, Loraine Cornwel, Daniel Rosen, Li Zhen Song, Silke Paust, Gretchen Diehl, David CorryFarrah Kheradmand

Pulmonary Medicine

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

Somatic mutations can promote malignant transformation of airway epithelial cells and induce inflammatory responses directed against resultant tumors. Tumor-infiltrating T lymphocytes (TIL) in early-stage non-small cell lung cancer (NSCLC) secrete distinct proinflammatory cytokines, but the contribution of these TILs to tumor development and metastasis remains unknown. We show here that TILs in early-stage NSCLC are biased toward IL17A expression (Th17) when compared with adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor infiltrating locoregional lymph nodes in advanced NSCLC. Mice in which Pten and Smad4 (Pts4d/d) are deleted from airway epithelial cells develop spontaneous tumors, that share genetic signatures with squamous- (SQ.2b), and adeno- (AD.1) subtypes of human NSCLC. Pts4d/d mice globally lacking in IL17a (Pts4d/dIl17a-/-) showed decreased tumor latency and increased metastasis. Th17 cells were required for recruitment of CD103ndritic cells, and adoptive transfer of IL17a-sufficient CD4cells reversed early tumor development and metastasis in Pts4d/dIl17a-/- mice. Together, these findings support a key role for Th17 cells in TILs associated with the Pts4d/d model of NSCLC and suggest therapeutic and biomarker strategies for human SQ2b and AD1 lung cancer. Cancer Immunol Res; 6(6); 645-57.

Original language	English (US)
Pages (from-to)	645-657
Number of pages	13
Journal	Cancer Immunology Research
Volume	6
Issue number	6
DOIs	https://doi.org/10.1158/2326-6066.CIR-17-0554
State	Published - Jun 2018

ASJC Scopus subject areas

Immunology
Cancer Research

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You, R., DeMayo, F. J., Liu, J., Cho, S. N., Burt, B. M., Creighton, C. J., Casal, R. F., Lazarus, D. R., Lu, W., Tung, H. Y., Yuan, X., Hill-McAlester, A., Kim, M., Perusich, S., Cornwel, L., Rosen, D., Song, L. Z., Paust, S., Diehl, G., ... Kheradmand, F. (2018). IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer. Cancer Immunology Research, 6(6), 645-657. https://doi.org/10.1158/2326-6066.CIR-17-0554

You, R, DeMayo, FJ, Liu, J, Cho, SN, Burt, BM, Creighton, CJ, Casal, RF, Lazarus, DR, Lu, W, Tung, HY, Yuan, X, Hill-McAlester, A, Kim, M, Perusich, S, Cornwel, L, Rosen, D, Song, LZ, Paust, S, Diehl, G, Corry, D & Kheradmand, F 2018, 'IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer', Cancer Immunology Research, vol. 6, no. 6, pp. 645-657. https://doi.org/10.1158/2326-6066.CIR-17-0554

@article{059134ec33f6464791f7b982f900292d,

title = "IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer",

abstract = "Somatic mutations can promote malignant transformation of airway epithelial cells and induce inflammatory responses directed against resultant tumors. Tumor-infiltrating T lymphocytes (TIL) in early-stage non-small cell lung cancer (NSCLC) secrete distinct proinflammatory cytokines, but the contribution of these TILs to tumor development and metastasis remains unknown. We show here that TILs in early-stage NSCLC are biased toward IL17A expression (Th17) when compared with adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor infiltrating locoregional lymph nodes in advanced NSCLC. Mice in which Pten and Smad4 (Pts4d/d) are deleted from airway epithelial cells develop spontaneous tumors, that share genetic signatures with squamous- (SQ.2b), and adeno- (AD.1) subtypes of human NSCLC. Pts4d/d mice globally lacking in IL17a (Pts4d/dIl17a-/-) showed decreased tumor latency and increased metastasis. Th17 cells were required for recruitment of CD103ndritic cells, and adoptive transfer of IL17a-sufficient CD4cells reversed early tumor development and metastasis in Pts4d/dIl17a-/- mice. Together, these findings support a key role for Th17 cells in TILs associated with the Pts4d/d model of NSCLC and suggest therapeutic and biomarker strategies for human SQ2b and AD1 lung cancer. Cancer Immunol Res; 6(6); 645-57.",

author = "Ran You and DeMayo, {Francesco J.} and Jian Liu and Cho, {Sung Nam} and Burt, {Bryan M.} and Creighton, {Chad J.} and Casal, {Roberto F.} and Lazarus, {Donald R.} and Wen Lu and Tung, {Hui Ying} and Xiaoyi Yuan and Andrea Hill-McAlester and Myunghoo Kim and Sarah Perusich and Loraine Cornwel and Daniel Rosen and Song, {Li Zhen} and Silke Paust and Gretchen Diehl and David Corry and Farrah Kheradmand",

note = "Funding Information: R.F. Casal reports receiving commercial research grants from Olympus, Siemens, and Concordia and is a consultant/advisory board member for Olympus. No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: {\textcopyright} 2018 AACR.",

year = "2018",

month = jun,

doi = "10.1158/2326-6066.CIR-17-0554",

language = "English (US)",

volume = "6",

pages = "645--657",

journal = "Cancer Immunology Research",

issn = "2326-6066",

publisher = "American Association for Cancer Research Inc.",

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T1 - IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer

AU - You, Ran

AU - DeMayo, Francesco J.

AU - Liu, Jian

AU - Cho, Sung Nam

AU - Burt, Bryan M.

AU - Creighton, Chad J.

AU - Casal, Roberto F.

AU - Lazarus, Donald R.

AU - Lu, Wen

AU - Tung, Hui Ying

AU - Yuan, Xiaoyi

AU - Hill-McAlester, Andrea

AU - Kim, Myunghoo

AU - Perusich, Sarah

AU - Cornwel, Loraine

AU - Rosen, Daniel

AU - Song, Li Zhen

AU - Paust, Silke

AU - Diehl, Gretchen

AU - Corry, David

AU - Kheradmand, Farrah

N1 - Funding Information: R.F. Casal reports receiving commercial research grants from Olympus, Siemens, and Concordia and is a consultant/advisory board member for Olympus. No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: © 2018 AACR.

PY - 2018/6

Y1 - 2018/6

N2 - Somatic mutations can promote malignant transformation of airway epithelial cells and induce inflammatory responses directed against resultant tumors. Tumor-infiltrating T lymphocytes (TIL) in early-stage non-small cell lung cancer (NSCLC) secrete distinct proinflammatory cytokines, but the contribution of these TILs to tumor development and metastasis remains unknown. We show here that TILs in early-stage NSCLC are biased toward IL17A expression (Th17) when compared with adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor infiltrating locoregional lymph nodes in advanced NSCLC. Mice in which Pten and Smad4 (Pts4d/d) are deleted from airway epithelial cells develop spontaneous tumors, that share genetic signatures with squamous- (SQ.2b), and adeno- (AD.1) subtypes of human NSCLC. Pts4d/d mice globally lacking in IL17a (Pts4d/dIl17a-/-) showed decreased tumor latency and increased metastasis. Th17 cells were required for recruitment of CD103ndritic cells, and adoptive transfer of IL17a-sufficient CD4cells reversed early tumor development and metastasis in Pts4d/dIl17a-/- mice. Together, these findings support a key role for Th17 cells in TILs associated with the Pts4d/d model of NSCLC and suggest therapeutic and biomarker strategies for human SQ2b and AD1 lung cancer. Cancer Immunol Res; 6(6); 645-57.

AB - Somatic mutations can promote malignant transformation of airway epithelial cells and induce inflammatory responses directed against resultant tumors. Tumor-infiltrating T lymphocytes (TIL) in early-stage non-small cell lung cancer (NSCLC) secrete distinct proinflammatory cytokines, but the contribution of these TILs to tumor development and metastasis remains unknown. We show here that TILs in early-stage NSCLC are biased toward IL17A expression (Th17) when compared with adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor infiltrating locoregional lymph nodes in advanced NSCLC. Mice in which Pten and Smad4 (Pts4d/d) are deleted from airway epithelial cells develop spontaneous tumors, that share genetic signatures with squamous- (SQ.2b), and adeno- (AD.1) subtypes of human NSCLC. Pts4d/d mice globally lacking in IL17a (Pts4d/dIl17a-/-) showed decreased tumor latency and increased metastasis. Th17 cells were required for recruitment of CD103ndritic cells, and adoptive transfer of IL17a-sufficient CD4cells reversed early tumor development and metastasis in Pts4d/dIl17a-/- mice. Together, these findings support a key role for Th17 cells in TILs associated with the Pts4d/d model of NSCLC and suggest therapeutic and biomarker strategies for human SQ2b and AD1 lung cancer. Cancer Immunol Res; 6(6); 645-57.

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IL17A regulates tumor latency and metastasis in lung adenoand squamous SQ.2band AD.1 cancer

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