Lu, Xin

Liu, Xia

Celià-Terrassa, Toni

Ren, Guangwen

Frontiers in Immunology

English

PubMed

Xin Lu

Xia Liu

Toni Celià-Terrassa

Guangwen Ren

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Editorial: Stromal and immune microenvironment in breast cancer metastasis

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The Jackson Laboratory: The Mouseion at the JAXlibrary

The Jackson Laboratory The Mouseion at the JAXlibrary Faculty Research 2022 Faculty Research 1-1-2022 Editorial: Stromal and immune microenvironment in breast cancer metastasis. Xin Lu Xia Liu Toni Celià-Terrassa Guangwen Ren Follow this and additional works at: https://mouseion.jax.org/stfb2022  Part of the Life Sciences Commons, and the Medicine and Health Sciences Commons Editorial: Stromal and immunemicroenvironment in breastcancer metastasisXin Lu1,2*, Xia Liu3, Toni Celià-Terrassa4 and Guangwen Ren51Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases,Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, United States,2Tumor Microenvironment and Metastasis Program, Indiana University Melvin and Bren SimonComprehensive Cancer Center, Indianapolis, IN, United States, 3Department of Toxicology andCancer Biology, Markey Cancer Center, College of Medicine, University of Kentucky, Lexington,KY, United States, 4Cancer Research Program, Hospital del Mar Medical Research Institute,Barcelona, Spain, 5The Jackson Laboratory, Bar Harbor, ME, United StatesKEYWORDSbreast cancer metastasis, chronic inflammation, eosinophil, tumor necrosis factor,cuproptosis, single-cell multiomicsEditorial on the Research TopicStromal and immune microenvironment in breast cancer metastasisBreast cancer is the most common cancer type in women and breast cancer-relateddeaths are mainly due to the metastases of tumors to the distant vital organs including thelung, liver, bone and brain. In the past three decades, significant advances in breast cancermetastasis research have revealed intricate interactions between tumor cells and the tissuemicroenvironments that are essential for the development of organ metastatic lesions.Within both primary tumor and distant organ microenvironments, immune infiltratesand stromal cells are the major components. Through chemical or physical interactionswith breast cancer cells, these non-neoplastic cells play instrumental roles in theprogression and metastasis of breast cancer. Recent technological advances,particularly the high throughput sequencing and proteomics, make it possible to revealthe heterogeneity and complex interactions of stromal cells, immune infiltrates andtumor cells at the single cell and spatial levels. This Frontiers Research Topic entitled“Stromal and Immune Microenvironment in Breast Cancer Metastasis” has collated 5contributions from experts who are exploring the cancer-immune crosstalk and its role inthe disease progression and prognosis of metastatic breast cancer.Eosinophils as a minor population of granulocytes that infiltrate breast cancer have apoorly understood function in cancer progression, despite their known role in allergy andTh2 immunity. Cederberg et al. explored the role of eosinophils in breast cancermetastasis to lung by employing transgenic mouse models with hypereosinophilia(IL5Tg mice) and hypoeosinophilia (DdblGATA mice), as well as antibody-mediateddepletion of eosinophils (Cederberg et al., 2022). These transgenic mice were used as thehost to examine the growth of murine syngeneic mammary tumor cells EO771 in thelungs. Pulmonary metastasis formation was significantly reduced in IL5Tg miceFrontiers in Immunology frontiersin.org01OPEN ACCESSEDITED AND REVIEWED BYKaty Rezvani,University of Texas MD AndersonCancer Center, United States*CORRESPONDENCEXin Luxlu@nd.eduSPECIALTY SECTIONThis article was submitted toCancer Immunityand Immunotherapy,a section of the journalFrontiers in ImmunologyRECEIVED 21 November 2022ACCEPTED 28 November 2022PUBLISHED 06 December 2022CITATIONLu X, Liu X, Celià-Terrassa T and Ren G(2022) Editorial: Stromal and immunemicroenvironment in breastcancer metastasis.Front. Immunol. 13:1104362.doi: 10.3389/fimmu.2022.1104362COPYRIGHT© 2022 Lu, Liu, Celià-Terrassa and Ren.This is an open-access articledistributed under the terms of theCreative Commons Attribution License(CC BY). The use, distribution orreproduction in other forums ispermitted, provided the originalauthor(s) and the copyright owner(s)are credited and that the originalpublication in this journal is cited, inaccordance with accepted academicpractice. No use, distribution orreproduction is permitted which doesnot comply with these terms.TYPE EditorialPUBLISHED 06 December 2022DOI 10.3389/fimmu.2022.1104362compared to wild-type mice or DdblGATA mice. Concordantly,eos inophi l deple t ion acce le ra ted lung metas tas i s .Mechanistically, lung eosinophils were activated duringmetastasis development, and expressed activation markers andreleased eosinophil peroxidase to kill tumor cells. These resultsestablish a metastasis-suppressor role of eosinophils in breastcancer, illuminating a promising therapy for breast cancer lungmetastasis by triggering local eosinophil degranulation.Chronic inflammation is a hallmark of solid tumors. Inthe context of breast cancer, chronic inflammation appears tobe an important risk factor and a potential promoter for thedisease progression. Among the factors that regulate tissueinflammation, tumor necrosis factor family of ligands(TNFSFs) and receptors (TNFRSFs) have prominent roles.Ekstrand et al. explored the association between the levels ofTNFSFs/TNFRSFs and breast tissue density or local breastestradiol levels with a cohort of 73 women including 12 withbreast cancer, 42 healthy postmenopausal women with differentbreast densities, and 19 healthy premenopausal women. Amongthe 23 members of the TNFSF/TNFRSF families measured bymicrodialysis and proximity extension assay, the majority ofTNFSF and TNFRSF proteins were significantly upregulated inbreast cancer compared with normal adjacent breast tissue. Inhealthy postmenopausal women, dense breast tissue exhibited asimilar dysregulation pattern as breast cancer, when comparedwith the non-dense breasts. Furthermore, estradiol correlatedwith most of the TNFSF/TNFRSF members, which was furthersupported in ER+ breast cancer mouse model. This study revealsthe potential of the specific TNFSF/TNFRSF family members asbiomarkers for breast cancer prevention (especially forpostmenopausal women with dense breasts) and as therapeutictargets for estrogen-dependent breast cancer.Recently, non-apoptotic regulated cell death mechanisms areamong the most exciting fronts of cell biology research. Amongthese mechanisms, cuproptosis is copper-dependent regulatedcell death that relies on mitochondria respiration and exhibitsemerging roles in tumor progression and immune response. Shaet al. performed a comprehensive bioinformatics analysis toexplore the potential role of cuproptosis-related genes (CRGs) inthe tumor microenvironment of triple-negative breast cancer.The TCGA dataset and three GEO datasets were analyzedsystematically. Interestingly, two CRG clusters were identifiedthat correlated well with the inflamed (hot) immune infiltrationpattern and the immune-desert (cold) pattern of breast cancer.Whereas the high CRG scores were associated with the stromalactivation and immunosuppression, the low CRG scores wereassociated with high tumor mutation burden, immune activationand better survival. Based on this study, specific hypotheses canbe generated to interrogate the functions of the disparatelyscored CRG genes in breast cancer immunity andimmunotherapy response.Single-cell multiomics, especially single-cell RNAsequencing (scRNA-seq), is a transforming technology forbiological research, including breast cancer research. Tan et al.reviewed recent literature that profiled breast cancermicroenvironment with single-cell technologies (scRNA-seq,spatial transcriptomics, CyTOF) and revealed the vastlycomplex heterogeneity in the immune and non-immunecompartments and their functional states. A comprehensivetable was provided to summarize the major constitutional cellpopulations (CD4+ T cells, CD8+ T cells, B cells, macrophages,neutrophils, monocytes, cancer-associated fibroblasts), therefined cell subtypes and markers for each major population,and their functions in the regulation of tumor immunity. Withthe wealth of information reviewed and summarized in anaccessible format, this review article provides an excellentresource for readers interested in exploring the breast cancercellular heterogeneity in depth.The crosstalk among different cell populations in eitherchemical signaling or mechanical form represents one of themost complex and fascinating aspects of the tumormicroenvironment research. Deeper understanding of thetumor-immune and stroma-immune interactions may lead tonovel therapeutic avenues to enhance the current treatmentregimens especially immunotherapy. Tan et al. reviewed therecent literature on this subject in the context of breast cancermetastasis and categorized the findings to topics includinginvasion/intravasation, extravasation/colonization, pre-metastatic niche, survival in the vascular and lymphaticsystems, and therapy resistance. This review provides aroadmap for researchers in the breast cancer metastasis fieldto grasp the cutting-edge findings on this subject and to identifythe knowledge gaps for future studies.Overall, these publications in the Research Topic are expectedto advance our understanding of the microenvironmentalregulation of breast cancer metastasis and potentially lead toexciting new therapeutic opportunities for patients withmetastatic breast cancer.Author contributionsAll authors listed have made a substantial, direct, andintellectual contribution to the work and approved itfor publication.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that couldbe construed as a potential conflict of interest.Lu et al. 10.3389/fimmu.2022.1104362Frontiers in Immunology frontiersin.org02Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteedor endorsed by the publisher.Lu et al. 10.3389/fimmu.2022.1104362Frontiers in Immunology frontiersin.org03

Editorial: Stromal and immune microenvironment in breast cancer metastasis.

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Editorial: Stromal and immune microenvironment in breast cancer metastasis.

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