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Alterations in PD-L1+ Myeloid Cells and Immune Infiltration Are Associated with Atezolizumab and Paclitaxel Therapy
Kerim Bora Yilmaz1,2, Ece Tavukcuoglu3, Hamdullah Yanik3
1Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, 06800 Ankara, Turkey.
Abstract:
Background and Objectives: A combination of chemotherapy and immunotherapy may improve cancer treatment outcomes; however, determining which patient groups will benefit from immunotherapy is critical. Triple-negative breast cancer (TNBC) achieves limited benefit from immune checkpoint inhibitors (ICIs) and anti-PD-L1 blockade therapy. Materials and Methods: In this study, PD-L1 expression levels in myeloid-derived cells in the tumor microenvironment were determined in an experimental TNBC model. Results: Compared with tumor cells, granulocytes, monocytes, and macrophages had significantly higher PD-L1 expression. CD206+ tumor-associated macrophages (TAMs) expressed the highest level of PD-L1. PD-L1 positivity in TAMs was also significantly high in the lung, liver, lymph node, and spleen. Despite treatment initiation in late-stage tumorigenesis, the combination of paclitaxel and the anti-PD-L1 monoclonal antibody atezolizumab significantly reduced tumor growth. In addition, lung metastasis burden was reduced with combined treatment compared with chemotherapy or anti-PD-L1 monotherapy alone. Conclusions: As a result, alterations in PD-L1+ myeloid cells and immune infiltration can be associated with atezolizumab and paclitaxel therapy success in triple-negative breast cancer.
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