CD8 T Cell Immunity Blocks the Metastasis of Carcinogen-exposed Breast Cancer

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Jun 19

PMID 34144976

Citations 22

Authors

Kaiwen Li

Tiancheng Li

Zhaoyi Feng

Mei Huang

Lei Wei

Zhiyu Yan

Mark Long

Qiang Hu

Jianmin Wang

Song Liu

Dennis C Sgroi

Shadmehr Demehri

Affiliations

Soon will be listed here.

Abstract

The link between carcinogen exposure and cancer immunogenicity is unclear. Single exposure to 12-dimethylbenz[a]anthracene (DMBA) at puberty accelerated spontaneous breast carcinogenesis in mouse mammary tumor virus-polyoma middle tumor-antigen transgenic (MMTV-PyMT or PyMT) and MMTV-Her2/neu (Her2) mice. Paradoxically, DMBA-treated PyMT and Her2 animals were protected from metastasis. CD8 T cells significantly infiltrated DMBA-exposed breast cancers. CD8 T cell depletion resulted in severe lung and liver metastasis in DMBA-treated PyMT mice. Besides increasing tumor mutational burden, DMBA exposure up-regulated Chemokine (C-C motif) ligand 21 (CCL21) in cancer cells and heightened antigen presentation. CCL21 injection suppressed breast cancer growth, and CCL21 receptor deletion attenuated T cell immunity against cancer metastasis in DMBA-treated PyMT animals. expression correlated with increased mutational burden and cytolytic activity across human cancers. Higher CCL21 levels correlated with increased CD8 T cell infiltrates in human breast cancer and predicted lower breast cancer distant recurrence rate. Collectively, carcinogen exposure induces immune-activating factors within cancer cells that promote CD8 T cell immunity against metastasis.

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References

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Vargo-Gogola T, Rosen J . Modelling breast cancer: one size does not fit all. Nat Rev Cancer. 2007; 7(9):659-72. DOI: 10.1038/nrc2193. View

Karolchik D, Hinrichs A, Furey T, Roskin K, Sugnet C, Haussler D . The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 2003; 32(Database issue):D493-6. PMC: 308837. DOI: 10.1093/nar/gkh103. View

Plitas G, Konopacki C, Wu K, Bos P, Morrow M, Putintseva E . Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer. Immunity. 2016; 45(5):1122-1134. PMC: 5134901. DOI: 10.1016/j.immuni.2016.10.032. View

Wang K, Li M, Hakonarson H . ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010; 38(16):e164. PMC: 2938201. DOI: 10.1093/nar/gkq603. View

Demehri S, Cunningham T, Manivasagam S, Ngo K, Moradi Tuchayi S, Reddy R . Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis. J Clin Invest. 2016; 126(4):1458-70. PMC: 4811115. DOI: 10.1172/JCI83724. View

Cristescu R, Mogg R, Ayers M, Albright A, Murphy E, Yearley J . Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science. 2018; 362(6411). PMC: 6718162. DOI: 10.1126/science.aar3593. View

Samanta S, Singh O, Jain R . Polycyclic aromatic hydrocarbons: environmental pollution and bioremediation. Trends Biotechnol. 2002; 20(6):243-8. DOI: 10.1016/s0167-7799(02)01943-1. View

Roh W, Chen P, Reuben A, Spencer C, Prieto P, Miller J . Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance. Sci Transl Med. 2017; 9(379). PMC: 5819607. DOI: 10.1126/scitranslmed.aah3560. View

10.

West N, Kost S, Martin S, Milne K, Deleeuw R, Nelson B . Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer. Br J Cancer. 2012; 108(1):155-62. PMC: 3553524. DOI: 10.1038/bjc.2012.524. View

11.

Hecht S . Lung carcinogenesis by tobacco smoke. Int J Cancer. 2012; 131(12):2724-32. PMC: 3479369. DOI: 10.1002/ijc.27816. View

12.

Bidwell B, Slaney C, Withana N, Forster S, Cao Y, Loi S . Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat Med. 2012; 18(8):1224-31. DOI: 10.1038/nm.2830. View

13.

Rizeq B, Malki M . The Role of CCL21/CCR7 Chemokine Axis in Breast Cancer Progression. Cancers (Basel). 2020; 12(4). PMC: 7226115. DOI: 10.3390/cancers12041036. View

14.

McCreery M, Halliwill K, Chin D, Delrosario R, Hirst G, Vuong P . Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat Med. 2015; 21(12):1514-20. PMC: 5094808. DOI: 10.1038/nm.3979. View

15.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

16.

DuPage M, Jacks T . Genetically engineered mouse models of cancer reveal new insights about the antitumor immune response. Curr Opin Immunol. 2013; 25(2):192-9. PMC: 3910114. DOI: 10.1016/j.coi.2013.02.005. View

17.

Griffith J, Sokol C, Luster A . Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014; 32:659-702. DOI: 10.1146/annurev-immunol-032713-120145. View

18.

Lee J, Lee M, Garon E, Goldman J, Salehi-Rad R, Baratelli F . Phase I Trial of Intratumoral Injection of Gene-Modified Dendritic Cells in Lung Cancer Elicits Tumor-Specific Immune Responses and CD8 T-cell Infiltration. Clin Cancer Res. 2017; 23(16):4556-4568. PMC: 5599263. DOI: 10.1158/1078-0432.CCR-16-2821. View

19.

Yang P, Li Q, Feng Y, Zhang Y, Markowitz G, Ning S . TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma. Cancer Cell. 2012; 22(3):291-303. PMC: 3443566. DOI: 10.1016/j.ccr.2012.07.023. View

20.

DeNardo D, Barreto J, Andreu P, Vasquez L, Tawfik D, Kolhatkar N . CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009; 16(2):91-102. PMC: 2778576. DOI: 10.1016/j.ccr.2009.06.018. View