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Editor | Xi In recent years, immunotherapy drugs represented by Immune Checkpoint Inhibitors (ICB) have achieved great success in the treatment of various tumors, greatly improving the survival rate and quality of life of some tumor patients.
Recent breast cancer clinical trial data show that ICB combined with neoadjuvant chemotherapy can improve patients' complete remission rate and event-free survival rate, and ICB single-agent neoadjuvant therapy is also expected to become one of the routine options for breast cancer treatment.
However, compared with melanoma and lung cancer, ICB therapy represented by anti-PD-1/PD-L1 antibody has not performed satisfactorily in the treatment of breast cancer.
It is urgent to further study the reasons and reasons for patients' lack of response to these drugs.
Develop new methods for predicting the population benefiting from neoadjuvant therapy to guide precision medicine practice.
On May 6, 2021, Researcher Qian Junbin from the Obstetrics and Gynecology Hospital of Zhejiang University School of Medicine, Professor Ann Smeets from Leuven University Hospital in Belgium, and Professor Diether Lambrechts from the VIB Institute published an article A single-cell map of Nature Medicine intratumoral changes during anti-PD1 treatment of patients with breast cancer.
The study conducted a "window of opportunity" clinical trial for breast cancer patients, that is, 29 newly diagnosed patients and 11 patients undergoing neoadjuvant chemotherapy were given anti-PD-1 antibodies for about 10 days after fine-needle biopsy of tumors.
Treatment, and then surgical removal of the mass, and perform single-cell transcriptome combined immunorepository sequencing (scRNA-seq + scTCR-seq) and single-cell transcriptome combined protein sequencing (CITE) on the biopsy before and after immunotherapy and postoperative tumor tissue.
-seq), and analyzed the changes of cellular components in the tumor microenvironment before and after immunotherapy, so as to identify specific cell types that potentially contribute to the outcome of immunotherapy, especially cell subtypes associated with T cell clonal proliferation.
By comparing the changes in the immune microenvironment of patients with and without clonal proliferation before and after treatment, this study reveals the differentiation rules of various immune cells in immunotherapy and the possible mechanism of action.
As the study suggests, the CD4+ and CD8+ T cell subtypes expressing PD-1 are the main target cells for anti-PD-1 therapy.
Among them, the degree of differentiation of the lineages corresponding to CD8+ TEX cells and helper CD4+ T cells (TH1, TFH) and Clonal proliferation can be used to predict the response of PD-1 treatment, and PD-1 treatment may further promote the differentiation of such cells.
In addition, macrophages such as CCR2+ or MMP9+ and various dendritic cell subtypes are positively correlated with treatment response, while the proportion of CX3CR1+ macrophages is negatively correlated with the clonal proliferation of T cells.
The study further found that the main cell types expressing PD-L1 in breast cancer are not tumor cells but macrophages and dendritic cells, and the high expression of PD-L1 in the latter two can predict immunotherapy response.
Finally, the research has discovered biomarkers that can predict immunotherapy response through bio-information analysis, and is expected to be applied in the practice of clinical treatment stratification for screening potential benefit populations.
This clinical study is different from previous immunotherapy studies in that it captures a short time window of about 10 days before and after immunotherapy.
The observation of the initial characteristics of the tumor microenvironmental changes induced by immunotherapy is our comprehensive understanding of the entire course of immunotherapy.
The key component of the mechanism of action has great guiding significance for clinical practice.
This new research model is also expected to be applied to the research of a variety of other tumors and even different diseases in the future.
Researcher Qian Junbin from the Obstetrics and Gynecology Hospital of Zhejiang University School of Medicine, Professor Ann Smeets from Leuven University Hospital in Belgium, and Professor Diether Lambrechts from the VIB Institute of Belgium are the co-corresponding authors of this study; from VIB Institute of Belgium and Leuven University Hospital, respectively PhD students Ayse Bassez and Hanne Vos are the co-first authors of this study.
Original link: Free PDF link: https://rdcu.
be/cj6zn Reprint Instructions [Non-original article] The copyright of this article belongs to the author of the article, welcome Personal reposting and sharing, reprinting without permission is prohibited, the author has all legal rights, offenders must be investigated.
Recent breast cancer clinical trial data show that ICB combined with neoadjuvant chemotherapy can improve patients' complete remission rate and event-free survival rate, and ICB single-agent neoadjuvant therapy is also expected to become one of the routine options for breast cancer treatment.
However, compared with melanoma and lung cancer, ICB therapy represented by anti-PD-1/PD-L1 antibody has not performed satisfactorily in the treatment of breast cancer.
It is urgent to further study the reasons and reasons for patients' lack of response to these drugs.
Develop new methods for predicting the population benefiting from neoadjuvant therapy to guide precision medicine practice.
On May 6, 2021, Researcher Qian Junbin from the Obstetrics and Gynecology Hospital of Zhejiang University School of Medicine, Professor Ann Smeets from Leuven University Hospital in Belgium, and Professor Diether Lambrechts from the VIB Institute published an article A single-cell map of Nature Medicine intratumoral changes during anti-PD1 treatment of patients with breast cancer.
The study conducted a "window of opportunity" clinical trial for breast cancer patients, that is, 29 newly diagnosed patients and 11 patients undergoing neoadjuvant chemotherapy were given anti-PD-1 antibodies for about 10 days after fine-needle biopsy of tumors.
Treatment, and then surgical removal of the mass, and perform single-cell transcriptome combined immunorepository sequencing (scRNA-seq + scTCR-seq) and single-cell transcriptome combined protein sequencing (CITE) on the biopsy before and after immunotherapy and postoperative tumor tissue.
-seq), and analyzed the changes of cellular components in the tumor microenvironment before and after immunotherapy, so as to identify specific cell types that potentially contribute to the outcome of immunotherapy, especially cell subtypes associated with T cell clonal proliferation.
By comparing the changes in the immune microenvironment of patients with and without clonal proliferation before and after treatment, this study reveals the differentiation rules of various immune cells in immunotherapy and the possible mechanism of action.
As the study suggests, the CD4+ and CD8+ T cell subtypes expressing PD-1 are the main target cells for anti-PD-1 therapy.
Among them, the degree of differentiation of the lineages corresponding to CD8+ TEX cells and helper CD4+ T cells (TH1, TFH) and Clonal proliferation can be used to predict the response of PD-1 treatment, and PD-1 treatment may further promote the differentiation of such cells.
In addition, macrophages such as CCR2+ or MMP9+ and various dendritic cell subtypes are positively correlated with treatment response, while the proportion of CX3CR1+ macrophages is negatively correlated with the clonal proliferation of T cells.
The study further found that the main cell types expressing PD-L1 in breast cancer are not tumor cells but macrophages and dendritic cells, and the high expression of PD-L1 in the latter two can predict immunotherapy response.
Finally, the research has discovered biomarkers that can predict immunotherapy response through bio-information analysis, and is expected to be applied in the practice of clinical treatment stratification for screening potential benefit populations.
This clinical study is different from previous immunotherapy studies in that it captures a short time window of about 10 days before and after immunotherapy.
The observation of the initial characteristics of the tumor microenvironmental changes induced by immunotherapy is our comprehensive understanding of the entire course of immunotherapy.
The key component of the mechanism of action has great guiding significance for clinical practice.
This new research model is also expected to be applied to the research of a variety of other tumors and even different diseases in the future.
Researcher Qian Junbin from the Obstetrics and Gynecology Hospital of Zhejiang University School of Medicine, Professor Ann Smeets from Leuven University Hospital in Belgium, and Professor Diether Lambrechts from the VIB Institute of Belgium are the co-corresponding authors of this study; from VIB Institute of Belgium and Leuven University Hospital, respectively PhD students Ayse Bassez and Hanne Vos are the co-first authors of this study.
Original link: Free PDF link: https://rdcu.
be/cj6zn Reprint Instructions [Non-original article] The copyright of this article belongs to the author of the article, welcome Personal reposting and sharing, reprinting without permission is prohibited, the author has all legal rights, offenders must be investigated.
