Circulating CD8 T-cell Repertoires Reveal the Biological Characteristics of Tumors and Clinical Responses to Chemotherapy in Breast Cancer Patients

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2018 Sep 1

PMID 30167861

Citations 17

Authors

Kai-Rong Lin

Dan-Mei Pang

Ya-Bin Jin

Qian Hu

Ying-Ming Pan

Jin-Huan Cui

Xiang-Ping Chen

Yin-Xin Lin

Xiao-Fan Mao

Hai-Bo Duan

Wei Luo

Affiliations

Soon will be listed here.

Abstract

Purpose: CD8 T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8 T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy.

Experimental Design: We applied a high-throughput TCR β-chain sequencing method to characterize the CD8 T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8 T-cell repertoire during chemotherapy were analyzed.

Results: We found that the HEC ratios of the CD8 T-cell repertoires from HER2 breast cancer patients were significantly higher than those of HER2 patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8 T cells. Several Vβ and CDR3 motifs preferentially used in HER2 patients were identified. Besides, we found that the circulating CD8 T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8 T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response.

Conclusions: Although functional studies of clonally expanded CD8 T-cell populations are clearly required, our results suggest that the circulating CD8 T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.

Citing Articles

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Yang J, Qiu L, Wang X, Chen X, Cao P, Yang Z Front Immunol. 2023; 14:1303491.

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References

Li W, Godzik A . Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics. 2006; 22(13):1658-9. DOI: 10.1093/bioinformatics/btl158. View

Luo W, Ma L, Wen Q, Zhou M, Wang X . Analysis of the conservation of T cell receptor alpha and beta chain variable regions gene in pp65 peptide-specific HLA-A*0201-restricted CD8+ T cells. Cell Mol Immunol. 2009; 6(2):105-10. PMC: 4002646. DOI: 10.1038/cmi.2009.14. View

Bai X, Zhang Q, Wu S, Zhang X, Wang M, He F . Characteristics of Tumor Infiltrating Lymphocyte and Circulating Lymphocyte Repertoires in Pancreatic Cancer by the Sequencing of T Cell Receptors. Sci Rep. 2015; 5:13664. PMC: 4556988. DOI: 10.1038/srep13664. View

Glanville J, Huang H, Nau A, Hatton O, Wagar L, Rubelt F . Identifying specificity groups in the T cell receptor repertoire. Nature. 2017; 547(7661):94-98. PMC: 5794212. DOI: 10.1038/nature22976. View

Freeman J, Warren R, Webb J, Nelson B, Holt R . Profiling the T-cell receptor beta-chain repertoire by massively parallel sequencing. Genome Res. 2009; 19(10):1817-24. PMC: 2765271. DOI: 10.1101/gr.092924.109. View

Luo W, Ma L, Wen Q, Wang N, Zhou M, Wang X . Analysis of the interindividual conservation of T cell receptor alpha- and beta-chain variable regions gene in the peripheral blood of patients with systemic lupus erythematosus. Clin Exp Immunol. 2008; 154(3):316-24. PMC: 2633227. DOI: 10.1111/j.1365-2249.2008.03770.x. View

Banerjee J, Schatz D . Synapsis alters RAG-mediated nicking at Tcrb recombination signal sequences: implications for the “beyond 12/23” rule. Mol Cell Biol. 2014; 34(14):2566-80. PMC: 4097660. DOI: 10.1128/MCB.00411-14. View

Jackisch C, Harbeck N, Huober J, von Minckwitz G, Gerber B, Kreipe H . 14th St. Gallen International Breast Cancer Conference 2015: Evidence, Controversies, Consensus - Primary Therapy of Early Breast Cancer: Opinions Expressed by German Experts. Breast Care (Basel). 2015; 10(3):211-9. PMC: 4569213. DOI: 10.1159/000433590. View

Muraro E, Martorelli D, Turchet E, Miolo G, Scalone S, Comaro E . A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies. Breast Cancer Res. 2011; 13(6):R117. PMC: 3326559. DOI: 10.1186/bcr3060. View

10.

Dieci M, Griguolo G, Miglietta F, Guarneri V . The immune system and hormone-receptor positive breast cancer: Is it really a dead end?. Cancer Treat Rev. 2016; 46:9-19. DOI: 10.1016/j.ctrv.2016.03.011. View

11.

Su S, Liao J, Liu J, Huang D, He C, Chen F . Blocking the recruitment of naive CD4 T cells reverses immunosuppression in breast cancer. Cell Res. 2017; 27(4):461-482. PMC: 5385617. DOI: 10.1038/cr.2017.34. View

12.

Schneider-Hohendorf T, Mohan H, Bien C, Breuer J, Becker A, Gorlich D . CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing. Nat Commun. 2016; 7:11153. PMC: 4822013. DOI: 10.1038/ncomms11153. View

13.

Park J, Jang M, Tarhan Y, Katagiri T, Sasa M, Miyoshi Y . Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy. Int J Oncol. 2016; 49(2):471-8. PMC: 4922832. DOI: 10.3892/ijo.2016.3540. View

14.

Emerson R, Sherwood A, Rieder M, Guenthoer J, Williamson D, Carlson C . High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire of tumour-infiltrating lymphocytes in ovarian cancer. J Pathol. 2013; 231(4):433-440. PMC: 5012191. DOI: 10.1002/path.4260. View

15.

Chen Z, Zhang C, Pan Y, Xu R, Xu C, Chen Z . T cell receptor β-chain repertoire analysis reveals intratumour heterogeneity of tumour-infiltrating lymphocytes in oesophageal squamous cell carcinoma. J Pathol. 2016; 239(4):450-8. DOI: 10.1002/path.4742. View

16.

Perez S, Karamouzis M, Skarlos D, Ardavanis A, Sotiriadou N, Iliopoulou E . CD4+CD25+ regulatory T-cell frequency in HER-2/neu (HER)-positive and HER-negative advanced-stage breast cancer patients. Clin Cancer Res. 2007; 13(9):2714-21. DOI: 10.1158/1078-0432.CCR-06-2347. View

17.

Chen Y, Xu Y, Zhao M, Liu Y, Gong M, Xie C . High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC. Oncoimmunology. 2016; 5(10):e1219010. PMC: 5087304. DOI: 10.1080/2162402X.2016.1219010. View

18.

Luo W, He W, Wen Q, Chen S, Wu J, Chen X . Changes of TCR repertoire diversity in colorectal cancer after Erbitux (cetuximab) in combination with chemotherapy. Am J Cancer Res. 2014; 4(6):924-33. PMC: 4266724. View

19.

Riaz N, Havel J, Makarov V, Desrichard A, Urba W, Sims J . Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab. Cell. 2017; 171(4):934-949.e16. PMC: 5685550. DOI: 10.1016/j.cell.2017.09.028. View

20.

Page D, Yuan J, Redmond D, Wen Y, Durack J, Emerson R . Deep Sequencing of T-cell Receptor DNA as a Biomarker of Clonally Expanded TILs in Breast Cancer after Immunotherapy. Cancer Immunol Res. 2016; 4(10):835-844. PMC: 5064839. DOI: 10.1158/2326-6066.CIR-16-0013. View