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

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.