Many studies have shown a special interaction between LAG3 and PD-1 in T cell inhibition, while the co-expression and effect of LAG3 and PD-1 on T cells in breast cancer patients are still not very clear. Here, with strict exclusion criteria, 88 patients with breast cancer and 18 healthy controls were enrolled. The percentages of LAG3+PD-1+ T cells in their peripheral blood (PBL) and tumor infiltrating T cells (TIL) were analyzed by flow cytometry, which showed an increase in TILs but no difference in PBLs and presented differences in TILs in different molecular subtypes (P < 0.05). In triple-negative breast cancer (TNBC), the highest percentages were observed, while in ER+/PR+ breast cancer, the lowest percentages were observed; however, these percentages were not different in different clinical stages (P > 0.05). Immunohistochemical staining showed that the expression of their ligands, PD-L1, MHC class II molecular and FGL1, was inconsistent in different molecular subtypes and clinical stages. Analysis of the functions of T cells with different phenotypes showed that the proliferation and secretion capacity of LAG3+PD-1+ T cells was obviously exhausted, with more than a two-fold of decrease compared with the groups of single positive LAG3 or PD-1 (P < 0.05). Finally, in a mouse model of TNBC, the dual blockade of LAG3 and PD-1 was indicated to achieve a better anti-tumour effect than either one alone (P < 0.05), which may provide a new strategy for the immunoregulatory treatment of patients with TNBC in the future.
Keywords: LAG3; PD-1; Synergistic inhibition; Triple-negative breast cancer; Tumour infiltrating lymphocytes.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.