Cancer Cell: Zhang Zemin's team and others reveal the mechanism of action of anti-PD-L1 immunotherapy combined with chemotherapy in triple-negative breast cancer

Breast cancer ranks first among female malignant tumors.

Although cancer immunotherapy has entered a period of rapid development, immunotherapy for triple-negative breast cancer is difficult: Although early clinical trials of IMpassion 130 have shown that anti-PD-L1 antibody Atezolizumab (Atezolizumab) combined with albumin-bound paclitaxel ( Nab-paclitaxel) can significantly reduce the risk of disease-free progression or death in patients with PD-L1+-negative breast cancer.

The differences in the results of different clinical trials suggest that different chemotherapeutic drugs may lead to different tumor microenvironment characteristics, which in turn affects the therapeutic effect of immune checkpoint inhibitors

On October 14, 2021, Peking University's Biomedical Frontier Innovation Center (BIOPIC) Zhang Zemin's research team, together with Liu Zhihua's research team, Ma Fei's and Xu Binghe's research team from the Cancer Hospital of the Chinese Academy of Medical Sciences, published an online publication on Cancer Cell, the top journal of oncology The research paper titled: Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple negative breast cancer

The researchers collected 78 paired samples from 22 triple-negative breast cancer patients (11 received atilizumab combined with paclitaxel chemotherapy, 11 received paclitaxel single-agent chemotherapy) before and after treatment, by integrating single-cell transcription Group sequencing, T cell receptor sequence sequencing, and chromatin accessibility sequencing have constructed high-resolution transcriptome and epigroup dynamic maps of the tumor microenvironment and peripheral blood-derived immune cells of triple-negative breast cancer patients

This study characterizes the immune cells of tumor tissue and peripheral blood from triple-negative breast cancer patients receiving two treatment options at the single-cell level, and systematically compares the tumor microenvironment and peripheral blood immune characteristics of responding and non-responding patients , Clarified the dynamic changes of immune cells under different treatment options, and revealed the mechanism of action of anti-PD-L1 immunotherapy combined with paclitaxel chemotherapy in triple-negative breast cancer

Figure 1 Project research plan and main conclusions

By comparing the differences in the composition of tumors and peripheral blood immune cells of different responders in the combination therapy group, the researchers found that the tumor microenvironment of the responding patients was enriched in two groups of T cells with high expression of CXCL13 (CD8-CXCL13 and CD4-CXCL13).

In addition, the researchers found that the tumor microenvironment of the responding patient was enriched in two groups of pro-inflammatory macrophages with high expression of CXCL9 and CXCL10, and there was a significant positive correlation between these two groups of pro-inflammatory macrophages and CXCL13+ T cells

The tumor microenvironment is a complex ecosystem, in which innate immune and adaptive immune cells, stromal cells, cancer cells and their interactions form a fine regulatory network that together determine the occurrence and development of cancer

By systematically characterizing the proportion and dynamic changes of immune cells, the researchers found that B cells, especially follicular B cells, were significantly enriched in the tumor microenvironment of responding patients, and they increased significantly after immunotherapy

In addition, based on the cell composition at the single cell level and the characteristic gene expression of TCGA public data, the researchers found that cDC1 is significantly positively correlated with CXCL13+T cells, and cDC1 is significantly increased under the action of immunotherapy, suggesting that cDC1 may be involved in CXCL13+T Activation of cells

The above findings indicate that paclitaxel chemotherapy regimens may weaken core anti-tumor immune cells, while immune checkpoint inhibitors can significantly increase core anti-tumor immune cells, suggesting that paclitaxel chemotherapy regimens can affect when combined with atilizumab The therapeutic effect of anti-PD-L1 antibody on patients with triple-negative breast cancer

This internationally leading novel work is by far the largest single-cell omics study on tumor-related immune cells of triple-negative breast cancer, in order to understand the immune characteristics of triple-negative breast cancer patients and the role of immunotherapy combined with chemotherapy regimens.

Dr.

Original source:

Yuanyuan Zhang, et al.