Triple-negative and HER2-overexpressing breast cancer cell sialylation impacts tumor microenvironment T-lymphocyte subset recruitment: a possible mechanism of tumor escape

Abstract

Christian Garbar,1,2 Corinne Mascaux,1,2 Yacine Merrouche,1,2 Armand Bensussan3 1Biopathology Department, Institut Jean Godinot – Unicancer, Reims, France; 2DERM-I-C EA7319, Université de Reims Champagne – Ardenne, Reims, France; 3INSERM U976; Université Paris Diderot, Sorbonne Paris Cité, Laboratory of Immunology, Dermatology & Oncology, Paris, France Introduction: Breast cancers develop different patterns of sialylation to modulate their tumor-infiltrating lymphocyte (TIL) environment. We studied the relationship between α-2,6 sialyltransferases and the TIL in different breast cancer molecular subgroups. Materials and methods: Immunohistochemical preparations were made from 39 luminal (LUM), 13 human epidermal growth factor receptor 2-overexpressing (HER2) and 47 triple-negative (TN) breast carcinomas. Targeted proteins included ST6Gal-I, ST6Gal-II, ST6GalNac-I, CD8, CD4 and granzyme-B in both cytotoxic T lymphocytes and NK lymphocytes (CTL/NK). Results: CTL/NK populations were significantly more frequent in TN than LUM (P <0.001). TN showed a lower level of ST6Gal-I expression than LUM or HER2 (both P > 0.001). ST6GalNac-I expression was lower in LUM than in TN or HER2 (P = 0.002 and P = 0.02, respectively). In HER2, a significant association was found between a low level of ST6Gal-I expression and a high TIL level. In TN, a significant association was observed between a high level of ST6Gal-II expression and a high TIL level. Conclusion: An increase in infiltrating lymphocytes could be influenced by low expression of ST6Gal-I in HER2 and by high expression of ST6Gal-II in TN breast cancers. Thus, targeting these sialylation pathways could modulate the levels of TIL. Keywords: breast, carcinoma, sialyltransferase, triple-negative, HER2

Keywords

• Breast
• carcinoma
• sialyltransferase
• triple-negative
• HER2