Tumor microenvironment characteristics of patients with different responses in the immunotherapy combined with chemotherapy group (photo courtesy of Zhang Zemin)
Tumor microenvironment characteristics of patients with different responses in the immunotherapy combined with chemotherapy group (photo courtesy of Zhang Zemin) Breast cancer ranks first among female malignancies, and triple-negative breast cancer (TNBC) is the subtype of breast cancer with the highest recurrence rate and mortality rate
On October 14, the international journal Cancer Cell published online research papers on Chinese scholars
Cancer Cell Zhang Zemin, one of the authors of the paper and a professor at Peking University’s Biomedical Frontier Innovation Center, told China Science Daily that this internationally leading novel work is the largest single-cell omics study on TNBC tumor-related immune cells in the world to date.
Although the early clinical trials of IMpassion 130 showed that the PD-L1 antibody Atezolizumab (Atezolizumab) combined with albumin-bound paclitaxel (Nab-paclitaxel) can significantly reduce the risk of disease-free progression or death in PD-L1+ TNBC patients, but the recent IMpassion 131 clinical trials have shown that atilizumab combined with paclitaxel does not benefit TNBC patients
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
This project collected 78 matched samples from 22 TNBC patients (11 received atelizumab combined with paclitaxel chemotherapy, 11 received paclitaxel single-agent chemotherapy), and integrated single-cell transcriptome sequencing and T cell receptor sequences.
By comparing the differences in the immune cell composition of different responders in the combination drug group, the researchers found that the tumor microenvironment of the responding patients was enriched in two groups of high-expressing CXCL13 T cells (CD8-CXCL13 and CD4-CXCL13), both of which were high at the same time.
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.
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 response to CXCL13+ T cells in the tumor microenvironment of the patient, and cause macrophages with immunosuppressive function.
In summary, the study revealed the molecular mechanism of TNBC patients' sensitivity and resistance to PD-L1 immunotherapy, identified key immune components and their dynamic changes under immune checkpoint inhibitors and paclitaxel chemotherapy regimens, and clarified paclitaxel chemotherapy The reason why the combined application with atelizumab cannot effectively increase the therapeutic effect of TNBC patients
The research was supported and funded by the Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, and the National Key Research and Development Program
Related paper information: https://doi.
https://doi.
org/10.
1016/j.
ccell.
2021.
09.
010
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