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

October 14, 2021, Biological forefront of innovation Medical Center (BIOPIC) Peking University, College of Life Sciences, Beijing future genetic diagnosis sophisticated Innovation Center (ICG) Zhang Zemin Task Force joint Chinese Academy of Medical Sciences Cancer Hospital Liu Zhihua Task Force, horse fly and Xu Bing River Task Force in the international journal Cancer Cell on the online form to Article published a report entitled Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple negative breast cancer research papers

Breast cancer ranks first among female malignant tumors.

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

The researchers collected 78 paired samples from 22 TNBC patients (11 received atilizumab combined with paclitaxel chemotherapy, 11 received paclitaxel single-agent chemotherapy) before and after treatment, and integrated single-cell transcriptome sequencing, T cell receptor sequence sequencing and chromatin access sequencing have constructed a high-resolution transcriptome and epigroup dynamic map of TNBC patients' tumor microenvironment and peripheral blood-derived immune cells

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 patients was enriched in two groups of pro-inflammatory macrophages with high expression of CXCL9 and CXCL10, andthere 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 constitute a fine regulatory network that together determine the occurrence and development of cancer

　　In summary, the study revealed the molecular mechanism of TNBC patients' sensitivity and resistance to anti-PD-L1 immunotherapy, identified key immune components and their dynamic changes under immune checkpoint inhibitors and paclitaxel chemotherapy regimens, and clarified The reason why paclitaxel chemotherapy combined with atelizumab cannot effectively increase the therapeutic effect of TNBC patients

　　This internationally leading novel work is the largest single-cell omics study on TNBC tumor-related immune cells so far, and provides a reliable foundation for in-depth understanding of the immune characteristics of TNBC patients and the mechanism of action of immunotherapy combined with chemotherapy.

　　Link to the paper: https://