Different cells and mediators in the tumor microenvironment play important roles in the progression of breast cancer. The aim of this study was to determine the composition of the microenvironment during tumor progression in order to discover new related biomarkers and potentials for targeted therapy.
In this study, breast cancer biopsies from four different stages, and control breast biopsies were collected. Then, the mRNA expression of several markers related to different CD4+ T cell subsets including regulatory T cells (Treg), T helper (Th) type 1, 2 and 17 were determined. In addition, we investigated the expression of two inflammatory cytokines (TNF-α and IL-6) and inflammatory mediators including FASL, IDO, SOCS1, VEGF, and CCR7.
The results showed that the expression of Th1 and Th17 genes was decreased in tumor tissues compared to control tissues. In addition, we found that the gene expression related to these two cell subsets decreased during cancer progression. Moreover, the expression level of TNF-α increased with tumor progression.
We conclude that the expression of genes related to immune response and inflammation is different between tumor tissues and control tissues. In addition, this difference was perpetuated through the different stages of cancer.
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8 + tumor-infiltrating lymphocytes and a high CD8 +/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA. 2005;102(51):18538–43. CrossRefPubMedPubMedCentral
Baharlou R, Atashzar MR, Vasmehjani AA, Rahimi E, Khoshmirsafa M, Seif F, Mahdiyar M. Reduced levels of T-helper 17-associated cytokines in the serum of patients with breast cancer: indicators for following the course of disease. CentralEur J Immunol. 2016;41(1):78–85. CrossRef
De La Cruz LM, Nocera NF, Czerniecki BJ. Restoring anti-oncodriver Th1 responses with dendritic cell vaccines in HER2/neu-positive breast cancer: progress and potential. Immunotherapy. 2016;8(10):1219–32. CrossRef
Funada Y, Noguchi T, Kikuchi R, Takeno S, Uchida Y, Gabbert HE. Prognostic significance of CD8 + T cell and macrophage peritumoral infiltration in colorectal cancer. Oncol Rep. 2003;10(2):309–13. PubMed
Ramello MC, Boari JT, Canale FP, Mena HA, Negrotto S, Gastman B, Gruppi A, Rodriguez EV, Montes CL. Tumor-induced senescent T cells promote the secretion of pro-inflammatory cytokines and angiogenic factors by human monocytes/macrophages through a mechanism that involves Tim-3 and CD40L. Cell Death Dis. 2014;5:e1507. CrossRefPubMedPubMedCentral
Majidzadeh AK, Esmaeili R, Abdoli N. TFRC and ACTB as the best reference genes to quantify urokinase plasminogen activator in breast cancer. BMC Res Notes. 2011;4:215. CrossRef
Burkholder B, Huang RY, Burgess R, Luo S, Jones VS, Zhang W, Lv ZQ, Gao CY, Wang BL, Zhang YM, et al. Tumor-induced perturbations of cytokines and immune cell networks. Biochem Biophys Acta. 2014;1845(2):182–201. PubMed
Sheu BC, Lin RH, Lien HC, Ho HN, Hsu SM, Huang SC. Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in human cervical cancer. J Immunol (Baltimore, Md: 1950). 2001;167(5):2972–8. CrossRef
Liu S, Foulkes WD, Leung S, Gao D, Lau S, Kos Z, Nielsen TO. Prognostic significance of FOXP3 + tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res. 2014;16(5):432. CrossRefPubMedPubMedCentral
Bozza C, Fontanella C, Buoro V, Mansutti M, Aprile G. Novel antiangiogenic drugs for the management of breast cancer: new approaches for an old issue? Expert Rev Clin Pharmacol. 2015;8(2):1–15. CrossRef
- Study of the tumor microenvironment during breast cancer progression
Stacy de Lima
- BioMed Central
Neu im Fachgebiet Onkologie
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