Augmentation of Antitumour Function of Tumour-infiltrating Lymphocytes Against Triple-negative Breast Cancer by PD-1 Blockade

Abstract T-cell-based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumour effect of adoptive cell therapy along with programmed cell death protein 1 (PD-1) inhibitor on triple-negative breast cancer (TNBC). We isolated and expanded tumour infiltration lymphocytes (TILs) from TNBC mouse tumour tissues and adoptive TIL transfusion (TILs-ACT) was applied in combination with a PD-1 inhibitor to the TNBC mouse model. The pre- and post-therapy antitumour efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo. TILs exhibited higher IFN-γ and TNF-α secretion than conventional T cells. The TILs-ACT combined with PD-1 inhibitor promoted active T-cell infiltration into the tumour tissue and exerted a strong antitumour effect in an in vivo model. Additionally, the strategy could downregulate the expression of inhibitory marker PD-1 on TILs. Our results suggested that PD-1 blockade regulated T-cell exhaustion which synergised with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumours. These findings might be useful in developing a feasible and effective therapeutic approach for TNBC.