Stromal CD4+ and CD8+ T Cells in Human Breast Carcinomas. Its Correlation with Chemokine MIG/CXCL9


The interaction between some chemokines with tumoral and stromal cells can influence tumor progression. CXCL9, a monokine induced by interferon gamma (MIG), targets lymphocytes.The aim of our study was to identify and quantify CD4+ and CD8+ T cells in the stroma of human breast cancer and correlate them with the presence of MIG/CXCL9. In 58 specimens of human breast carcinoma and 10 normal breast tissue from mammoplasty surgery, immunohistochemistry and ELISA methods were performed. The number of CD4+ and CD8+ T cells in breast cancer tissue was significantly increased compared with normal breast tissue with a clear predominance of CD8+ T cells. MIG/CXCL9 levels were significantly elevated respect normal breast tissue. This chemokine correlated with the number of CD8+ T cells only in non-metastatic tumors. These data suggest that MIG targets cytotoxic T cells. Their recruitment into breast carcinoma can play a critical role in malignant progression, inhibiting the production of metastasis.

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Laguens, G. , Coronato, S. , Chambó, J. and Girolamo, V. (2012) Stromal CD4+ and CD8+ T Cells in Human Breast Carcinomas. Its Correlation with Chemokine MIG/CXCL9. Advances in Breast Cancer Research, 1, 7-11. doi: 10.4236/abcr.2012.12002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. B. Reome, J. C. Hylind, R. W. Dutton and M. J. Dobrzanski, “Type 1 and Type 2 Tumor Infiltrating Effector Cell Subpopulations in Progressive Breast Cancer,” Clinical Immunology, Vol. 111, No. 1, 2004, pp. 69-81.
[2] D. G. De Nardo and L. M. Coussens, “Balancing Immune Response: Crosstalk between Adaptative and Innate Immune Cells during Breast Cancer Progression,” Breast Cancer Research, Vol. 9, No. 4, 2007, pp. 212-222.
[3] A. Ben-Baruch, “The Multifaceted Roles of Chemokines in Malignancy,” Cancer and Metastasis Reviews, Vol. 25, No. 3, 2006, pp. 357-371.
[4] D. Raman, P. J. Baugher, Y. M. Thu and A. Richmond, “Role of Chemokines in Tumor Growth,” Cancer Letters, Vol. 256, No. 2, 2007, pp. 137-165.
[5] T. Tanaka, Z. Bai, Y. Srinoulprasert, B. G. Yang, H. Hayasaka and M. Miyasaka, “Chemokines in Tumor Progression and Metastasis,” Cancer Science, Vol. 96, No. 6, 2008, pp. 317-322. doi:10.1111/j.1349-7006.2005.00059.x
[6] M. L. Balestrieri, A. Balestrieri, F. P. Mancini and C. Napoli, “Understanding the Immunoangiostatic CXC Chemokine Network,” Cardiovascular Research, Vol. 78, No. 2, 2008, pp. 250-256.
[7] J. R. Groon and A. D. Luster, “CXC3 Ligand: Redundant, Collaborative and Antagonistic Functios,” Immunology and Cell Biology, Vol. 89, 2011, pp. 207-215. doi:10.1038/icb.2010.158
[8] A. E. Karnoub and R. Weinberg, “Chemokine Networks and Breast Cancer Metastasis,” Breast Disease, Vol. 26, No. 3-4, 2007, pp. 75-85.
[9] J. Vandercappellen, J. Van Damme and S. Struyf, “The Role of CXC Chemokines and Their Receptors in Cancer,” Cancer Letters, Vol. 267, No. 2, 2008, pp. 226-244.
[10] P. Allavena, G. Germano, F. Marchesi and A. Mantovani, “Chemokines in Cancer Related Inflammation,” Experimental Cell Research, Vol. 317, No. 5, 2011, pp. 664- 667.
[11] A. Mantovani, B. Savino, M. Locati, L. Zammataro, P. Allavena and R. Bonecchi, “The Chemokine System in Cancer Biology and Therapy,” Cytokine & Growth Factor Review, Vol. 21, No. 1, 2010, pp. 27-39.
[12] A. Ben-Baruch, “Pro-Malignancy and Putative Antimalignancy Chemokines in the Regulation of Breast Cancer Progression,” In: F. Columbus, Ed., Focus on Immunology Research, Nova Science Publishers, New York, 2006, pp. 1-46.
[13] T. C. Walser, S. Rifat, X. Ma, N. Kundu, C. Ward, O. Goloubeva et al., “Antagonism of CXCR3 Inhibits Lung Metastasis in a Murine Model of Metastatic Breast Cancer,” Cancer Research, Vol. 66, No. 15, 2006, pp. 7701- 7707. doi:10.1158/0008-5472.CAN-06-0709
[14] T. Walser, X. Ma, N. Kundu, R. Dorsey, O. Goloubeba, A. M. Fulton, “Immune Mediated Modulation of Breast Cancer Growth and Metastasis by the Chemokine Mig (CXCL9) in a Murine model,” Immunother, Vol. 30, No. 5, 2007, pp. 490-497.
[15] J. Valdivia-Silva, J. Franco-Barraza, A. Esparza Silva, G. Du Pont, G. Soldevila, I. Meza, et al., “Effect of Pro-In- flammatory Cytokine Stimulation on Human Breast Cancer: Implications of Chemokine Receptor Expression in Cancer Metastasis,” Cancer Letters, Vol. 283, No. 2, 2009, pp. 176-185.
[16] T. F. Gajewski, Y. Meng, C. Blank, et al., “Immune Resistance Orchestrated by the Tumor Microenvironment,” Immunological Reviews, Vol. 213, No. 1, 2006, pp. 131- 145.
[17] H. Harlin, Y. Meng, A. C. Peterson, et al., “Chemokine Expression in Melanoma Metastases Associated with CD8 + T-Cell Recruitment,” Cancer Research, Vol. 69, No. 3, 2009, pp. 3077-3085.
[18] H. Ohtani, Z. Jin, S. Takegawa, T. Nakayama and O. Yoshie, “Abundant Expression of CXCL9 (MIG) by Stromal Cells That Include Dendritic Cells and Accumulation of CXCR3+ T Cells in Lymphocyte-Rich Gastric Carcinoma,” The Journal of Pathology, Vol. 217, No. 1, 2009, pp. 21-31.
[19] H. Ohtani and O. Yoshie, “Morphometric Analysis of the Balance between CXCR3+ T Cells and FOXP3+ Regulatory T Cells in Lymphocyte-Rich and Conventional Gastric Cancers,” Virchows Arch, Vol. 456, No. 6, 2010, pp. 615-623.
[20] A. Fulton, F. Miller, A. Weise and W. Z. Wei, “Prospects of Controlling Breast Cancer Metastasis by Immune Intervention,” Breast Disease, Vol. 26, 2007, pp. 115-127.
[21] T. Kondo, H. Nakazawa, F. Ito, Y. Hashimoto, Y. Osaka, K. Futatsushama, et al., “Favorable Prognosis of Renal Cell Carcinoma with Increased Expression of Chemokines Associated with a Th1-Type Immune Response,” Cancer Science, Vol. 97, 2006, pp. 780-786. doi:10.1111/j.1349-7006.2006.00231.x
[22] W. Di Girolamo, S. Coronato, E. Portiansky and G. Laguens, “Profile of Immune Cells in Lymph Nodes Draining Human Malignant Tumors,” Medicina, Vol. 68, 2008, pp. 423-427.
[23] S. Hirano, Y. Iwashita, A. Sasaki, S. Kai, M. Ohta and S. Kitano, “Increased mRNA Expression of Chemokines in Hepatocellular Carcinoma with Tumor-Infiltrating Lymphocytes,” Journal of Gastroenterology and Hepatology, Vol. 22, No. 5, 2007, pp. 611-612.
[24] J. Yu, “Targeting Chemokines as a Therapeutic Option for Hepatocellular Carcinoma: A Reality or Just a Fantasy?” Journal of Gastroenterology and Hepatology, Vol. 22, 2007, pp. 611-612. doi:10.1111/j.1440-1746.2007.04970.x
[25] P. P. Leong, R. Mohammad, N. Ibrahim, H. Ithnin, M. Abdullah, W. C. Davis, et al., “Phenotyping of Lymphocytes Expressing Regulatory and Effector Markers in Infiltrating Ductal Carcinoma of the Breast,” Immunology Letters, Vol. 102, No. 2, 2006, pp. 229-236. doi:10.1016/j.imlet.2005.09.006

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