10.3389/fimmu.2020.00366.s002 Meizhuo Gao Meizhuo Gao Tie Wang Tie Wang Litong Ji Litong Ji Shuping Bai Shuping Bai Lining Tian Lining Tian Hongjiang Song Hongjiang Song Image_2_Therapy With Carboplatin and Anti-PD-1 Antibodies Before Surgery Demonstrates Sustainable Anti-Tumor Effects for Secondary Cancers in Mice With Triple-Negative Breast Cancer.TIFF Frontiers 2020 triple-negative breast cancer carboplatin immune checkpoint inhibitor surgery tumor microenvironment 2020-03-05 04:18:29 Figure https://frontiersin.figshare.com/articles/figure/Image_2_Therapy_With_Carboplatin_and_Anti-PD-1_Antibodies_Before_Surgery_Demonstrates_Sustainable_Anti-Tumor_Effects_for_Secondary_Cancers_in_Mice_With_Triple-Negative_Breast_Cancer_TIFF/11936568 <p>Patients with triple-negative breast cancer (TNBC) suffer an unfavorable prognosis. Carboplatin (CBDCA) as a cytotoxic reagent has been widely administered to patients with cancer including TNBC. Programmed cell death protein 1 (PD-1) is an immune checkpoint, blockade of which unleashes T cell functions that kill cancer cells. However, the efficacy of CBDCA combined with anti-PD-1 antibodies in TNBC has not been determined. Patient-derived xenografts (PDX) were implanted to immune-deficient mice. Three mouse TNBC cell lines (4T1, EMT6, and E0771) were seeded to immune-competent mice. Tumor volumes and survival rates were monitored. CBDCA and anti-PD-1 antibodies were administered by intra-peritoneal injection at designated time points. Total CD8<sup>+</sup> T cells, memory CD8<sup>+</sup> T cells, and CD103<sup>+</sup> dendritic cells (DC) in the tumor were measured by flow cytometry. Tumor-specific CD8<sup>+</sup> T cells were quantified by the ELISpot assay. Administration of CBDCA to PDX-bearing mice induced increased levels of tumor cell necrosis and reduced tumor size. Treatment with CBDCA and anti-PD-1 antibodies reduced TNBC tumor volumes and slightly improved survival rates. More importantly, therapy with CBDCA and anti-PD-1 antibodies before surgery showed a remarkably improved, sustainable protection against a secondary tumor after surgery by a CD8<sup>+</sup>- T-cell-dependent manner, which required CCL4 expressed in the tumor and subsequently CD103<sup>+</sup> DC recruited to the tumor microenvironment. Immunochemotherapy with CBDCA and anti-PD-1 antibodies before surgery improves the outcome of a secondary tumor after surgery via increasing the number of tumor-specific CD8<sup>+</sup> T cells in the tumor microenvironment of murine TNBC. These results highlight the possibility to utilize this regimen in clinical practice.</p>