Fudan University "Cancer Research" published a paper: Cancer stem cell markers promote breast cancer by reshaping the immune microenvironment

 More and more studies have shown that in a small part of a variety of tumor tissues, a small part of cells with particularly strong tumorigenicity, extremely low differentiation, and self-renewal and multidirectional differentiation characteristics of stem cells are called “cancer stem cells (Cancer Stem Cells).

 On December 1, 2021, Liu Suling’s team from our hospital published an online research paper entitled ALDH1A1 activity in tumor-initiating cells remodels myeloid-derived suppressor to promote breast cancer progression in Cancer Research , revealing that ALDH1A1 relies on its enzyme activity to promote breast cancer progression .

 In order to analyze the remodeling effect of ALDH1A1 on the immune microenvironment of breast cancer, the authors constructed a triple-negative breast cancer stable cell line that overexpressed wild-type ALDH1A1 (with enzyme activity) and K193Q/R mutant (with no enzyme activity).

 In terms of mechanism, they found that ALDH1A1 relies on its enzyme activity to lower the pH value in tumor cells, thereby activating the TAK1-NFkB signaling pathway, increasing the secretion of granulocyte macrophage stimulating factor (GM-CSF) in tumor cells, and then inducing the tumor microenvironment With the increase of MDSCs, the increase of MDSCs finally inhibited the anti-tumor immune activity of CD8+ T cells to promote breast tumor growth

 Aiming at the specific mechanism that ALDH1A1 exerts to promote breast cancer, they designed a combined treatment strategy to more efficiently target the treatment of malignant breast cancer

 Overall, this study found that ALDH1A1 relies on enzyme activity to reduce pHi in breast tumor cells to activate the TAK1-NFkB signaling pathway, which in turn leads to increased secretion of GM-CSF, induces MDSC amplification and reduces anti-tumor immunity, thereby promoting the development of breast tumors

 Doctoral student Liu Cuicui from the Cancer Hospital of Fudan University is the first author of the paper; Professor Liu Suling from the Institute of Biomedical Research/Affiliated Tumor Hospital of Fudan University, Associate Researcher Zhang Lixing from the Cancer Hospital of Fudan University, Professor Xiaoyong Zhang from the Institute of Brain Science of Fudan University and Tumor Affiliated to Fudan University Professor Shao Zhimin from the hospital is the co-corresponding author of this article

Link to the original text: https://cancerres.