Effect modification between HLA-F and CD56 markers reveals differences in survival for triple-negative breast cancer patients.

Triple-negative breast cancer (TNBC) is usually aggressive and challenging to treat. With high tumour immunogenicity TNBC patients might benefit from immunotherapy. We evaluated heterogeneous immune profiles of individual tumours in relation to clinical development to identify immune markers and their mutual expression. We assessed 122 biopsies from patients with primary TNBC tumours by automated image analysis of immunohistochemically stained tissue microarrays. Tumour-infiltrating lymphocytes (TILs), expression of HLA I molecules (HLA-ABC, HLA-G, HLA-E, HLA-F) and their mutual associations, as well as associations with other immune response markers (PD-L1, FOXP3, CD4, CD8, CD56) were investigated together with survival outcomes. Analysis of effect modification between HLA-F and CD56 showed longer disease-free survival and time-to-recurrence for tumours with low expression of both markers. TILs were significantly associated with tumour grade and with HLA-F, PD-L1, FOXP3 and CD8 expression, and were significantly associated with longer disease-free survival, also in multivariate analysis. Expression of all immune markers was positively correlated with each other, except CD56. The study highlights the complex immune regulation in TNBC stressing the importance of evaluating the immune landscape of individual tumours to identify patients that can benefit from immunotherapy. The finding of an effect modulation between HLA-F and CD56 is one aspect.