Sanghoon Lee, Youngbin Cho, Yiting Li, Ruxuan Li, Angela Wong Lau, Matthew S Laird, Daniel Brown, Priscilla McAuliffe, Adrian V Lee, Steffi Oesterreich, Ioannis K Zervantonakis, Hatice Ulku Osmanbeyoglu
{"title":"癌细胞衍生的 S100A11 可促进 ER+ 乳腺癌巨噬细胞的招募。","authors":"Sanghoon Lee, Youngbin Cho, Yiting Li, Ruxuan Li, Angela Wong Lau, Matthew S Laird, Daniel Brown, Priscilla McAuliffe, Adrian V Lee, Steffi Oesterreich, Ioannis K Zervantonakis, Hatice Ulku Osmanbeyoglu","doi":"10.1080/2162402X.2024.2429186","DOIUrl":null,"url":null,"abstract":"<p><p>Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors. We found that recombinant S100A11 enhances macrophage infiltration and migration in a dose-dependent manner. Additionally, in a 3D matrix using a panel of three ER+ breast cancer cell lines, we showed that secreted S100A11 levels from cancer cells were associated with increased monocyte infiltration that subsequently differentiation toward macrophages. Genetic silencing of S100A11 in the S100A11-high T47D cancer cells reduced monocyte infiltration, consistent with results using a S100A11 blocking antibody in T47D cancer cells and in a clinically relevant patient-derived organoid model. Phenotypic analysis of macrophages cocultured with T47D cancer cells following S100A11 knockdown revealed lower expression of the immunosuppressive marker CD206, further underscoring the role of S100A11 as a paracrine regulator of pro-tumorigenic cancer-macrophage crosstalk. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.</p>","PeriodicalId":48714,"journal":{"name":"Oncoimmunology","volume":"13 1","pages":"2429186"},"PeriodicalIF":6.5000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601052/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer.\",\"authors\":\"Sanghoon Lee, Youngbin Cho, Yiting Li, Ruxuan Li, Angela Wong Lau, Matthew S Laird, Daniel Brown, Priscilla McAuliffe, Adrian V Lee, Steffi Oesterreich, Ioannis K Zervantonakis, Hatice Ulku Osmanbeyoglu\",\"doi\":\"10.1080/2162402X.2024.2429186\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors. We found that recombinant S100A11 enhances macrophage infiltration and migration in a dose-dependent manner. Additionally, in a 3D matrix using a panel of three ER+ breast cancer cell lines, we showed that secreted S100A11 levels from cancer cells were associated with increased monocyte infiltration that subsequently differentiation toward macrophages. Genetic silencing of S100A11 in the S100A11-high T47D cancer cells reduced monocyte infiltration, consistent with results using a S100A11 blocking antibody in T47D cancer cells and in a clinically relevant patient-derived organoid model. Phenotypic analysis of macrophages cocultured with T47D cancer cells following S100A11 knockdown revealed lower expression of the immunosuppressive marker CD206, further underscoring the role of S100A11 as a paracrine regulator of pro-tumorigenic cancer-macrophage crosstalk. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.</p>\",\"PeriodicalId\":48714,\"journal\":{\"name\":\"Oncoimmunology\",\"volume\":\"13 1\",\"pages\":\"2429186\"},\"PeriodicalIF\":6.5000,\"publicationDate\":\"2024-12-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601052/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncoimmunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/2162402X.2024.2429186\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncoimmunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/2162402X.2024.2429186","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer.
Macrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors. We found that recombinant S100A11 enhances macrophage infiltration and migration in a dose-dependent manner. Additionally, in a 3D matrix using a panel of three ER+ breast cancer cell lines, we showed that secreted S100A11 levels from cancer cells were associated with increased monocyte infiltration that subsequently differentiation toward macrophages. Genetic silencing of S100A11 in the S100A11-high T47D cancer cells reduced monocyte infiltration, consistent with results using a S100A11 blocking antibody in T47D cancer cells and in a clinically relevant patient-derived organoid model. Phenotypic analysis of macrophages cocultured with T47D cancer cells following S100A11 knockdown revealed lower expression of the immunosuppressive marker CD206, further underscoring the role of S100A11 as a paracrine regulator of pro-tumorigenic cancer-macrophage crosstalk. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.
期刊介绍:
OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy.
As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology.
The journal covers a wide range of topics, including:
-Basic and translational studies in immunology of both solid and hematological malignancies
-Inflammation, innate and acquired immune responses against cancer
-Mechanisms of cancer immunoediting and immune evasion
-Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells
-Immunological effects of conventional anticancer therapies.