2. Academic Validation
  3. GSDME-mediated pyroptosis promotes anti-tumor immunity of neoadjuvant chemotherapy in breast cancer

GSDME-mediated pyroptosis promotes anti-tumor immunity of neoadjuvant chemotherapy in breast cancer

  • Cancer Immunol Immunother. 2024 Jul 2;73(9):177. doi: 10.1007/s00262-024-03752-z.
Changfang Fu # 1 2,  Wenbo Ji # 3,  Qianwen Cui 4,  Anling Chen 4,  Haiyan Weng 5,  Nannan Lu 6,  Wulin Yang 7 8
Affiliations

Affiliations

  • 1 Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
  • 2 Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparations and Clinical Pharmacy, Hefei, 230001, Anhui, China.
  • 3 Clinical Pharmacy Department, Anhui Provincial Children's Hospital, Hefei, 230000, Anhui, China.
  • 4 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
  • 5 Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
  • 6 Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. lnn279@ustc.edu.cn.
  • 7 Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China. yangw@cmpt.ac.cn.
  • 8 Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, China. yangw@cmpt.ac.cn.
  • # Contributed equally.
PMID: 38954046 DOI: 10.1007/s00262-024-03752-z
Abstract

Paclitaxel and anthracycline-based chemotherapy is one of the standard treatment options for breast Cancer. However, only about 6-30% of breast Cancer patients achieved a pathological complete response (pCR), and the mechanism responsible for the difference is still unclear. In this study, random forest algorithm was used to screen feature genes, and artificial neural network (ANN) algorithm was used to construct an ANN model for predicting the efficacy of neoadjuvant chemotherapy for breast Cancer. Furthermore, digital pathology, cytology, and Molecular Biology experiments were used to verify the relationship between the efficacy of neoadjuvant chemotherapy and immune ecology. It was found that paclitaxel and doxorubicin, an anthracycline, could induce typical Pyroptosis and bubbling in breast Cancer cells, accompanied by gasdermin E (GSDME) cleavage. Paclitaxel with LDH release and Annexin V/PI doubule positive cell populations, and accompanied by the increased release of damage-associated molecular patterns, HMGB1 and ATP. Cell coculture experiments also demonstrated enhanced phagocytosis of macrophages and increased the levels of IFN-γ and IL-2 secretion after paclitaxel treatment. Mechanistically, GSDME may mediate paclitaxel and doxorubicin-induced Pyroptosis in breast Cancer cells through the caspase-9/Caspase-3 pathway, activate anti-tumor immunity, and promote the efficacy of paclitaxel and anthracycline-based neoadjuvant chemotherapy. This study has practical guiding significance for the precision treatment of breast Cancer, and can also provide ideas for understanding molecular mechanisms related to the chemotherapy sensitivity.

Keywords

Breast cancer; Immunogenic cell death; Neoadjuvant chemotherapy; Pathological complete response; Pyroptosis.

Figures
Products