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

On October 14, 2021, Peking University Biomedical Frontier Innovation Center (BIOPIC), School of Life Sciences, Beijing Future Gene Diagnosis Advanced Innovation Center (ICG) Zhang Zemin's research group, and Chinese Academy of Medical Sciences Cancer Hospital Liu Zhihua's research group, Ma Feihe Xu Binghe’s research group published a research paper titled " Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple negative breast cancer " online in the international journal Cancer Cell in the form of Article .

Screenshot of the paper

Breast cancer ranks first among female malignant tumors.

Researchers on this subject 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, 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 TNBC patients’ tumor microenvironment and peripheral blood-derived immune cells

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).

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

By comparing the dynamic changes of immune cells in the chemotherapy group and the combination drug group, the researchers found that in contrast to the combination drug, paclitaxel single-agent chemotherapy can significantly reduce the CXCL13 ⁺ T cells in the tumor microenvironment of the responding patient , and lead to immune suppression.

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 in the world so far, providing a reliable understanding of the immune characteristics of TNBC patients and the mechanism of action of immunotherapy combined with chemotherapy.

Dr.