Triple negative breast cancer (TNBC) is aggressive and has a high propensity to metastasise. Currently there is no effective targeted therapy for TNBC, and most patients will develop resistance to chemotherapy, the conventional option available. Immunotherapy may provide an approach to control this disease. However, breast cancer has poor immunogenicity, in part due to impaired expression and presentation of MHC class-1, and expression of programmed cell death -1 ligand (PD-L1) and limited immune infiltration.
Accumulating evidence suggests that the matrix composition of breast tumour and the repertoire of surface adhesion receptors of cancer cells may play a role in immunogenic potency. Previous studies have shown that the extracellular matrix protein laminin 511 (LM-511) is produced abundantly in TNBC and is involved in metastatic progression. However, its role in immune-surveillance and immune-infiltration has yet to be determined.
Herein, we performed an immunohistochemical analysis of a syngeneic model of TNBC (4T1BM2) and demonstrate that genetic suppression of LM-511 results in significantly increased infiltration of CD8+ and CD4+ T cells into the mammary tumour. A trend towards increased infiltration of MPO+ve neutrophils, F4/80+ve macrophages and Foxp3+ve regulatory T cells was also observed. Using recombinant LM-511 and a unique laminin-511-binding antibody developed by our group, we provide proof of principle that secreted LM-511 may bind the surface of circulating tumour cells and increase their survival and proliferative potential in vitro. Lastly, we provide evidence that the presence of LM-511 on the surface of tumour cells may shield and partially protects them from immune cell killing.