scholarly journals Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Agnese Losurdo ◽  
Caterina Scirgolea ◽  
Giorgia Alvisi ◽  
Jolanda Brummelman ◽  
Valentina Errico ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Ex Vivo ◽  
Normal Breast ◽  
Tumor Control ◽  
Memory Cd8 T Cells ◽  
Heterogeneous Behavior ◽  
Single Cell Profiling ◽  
Adjacent Normal Breast Tissue

AbstractLuminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127− CD39hi Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39lo Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs.

scholarly journals Author Correction: Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Agnese Losurdo ◽  
Caterina Scirgolea ◽  
Giorgia Alvisi ◽  
Jolanda Brummelman ◽  
Valentina Errico ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Memory Cd8 T Cells ◽  
Single Cell Profiling

scholarly journals Single-Cell Transcriptomic Analysis of Tumor-Derived Fibroblasts and Normal Tissue-Resident Fibroblasts Reveals Fibroblast Heterogeneity in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1307 ◽  
Author(s):  
Aimy Sebastian ◽  
Nicholas R. Hum ◽  
Kelly A. Martin ◽  
Sean F. Gilmore ◽  
Ivana Peran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Mhc Class Ii ◽  
Smooth Muscle Actin ◽  
Class Ii ◽  
Normal Breast ◽  
Syngeneic Mouse Model ◽  
Elevated Expression ◽  
Tumor Types ◽  
Antigen Presenting

Cancer-associated fibroblasts (CAFs) are a prominent stromal cell type in solid tumors and molecules secreted by CAFs play an important role in tumor progression and metastasis. CAFs coexist as heterogeneous populations with potentially different biological functions. Although CAFs are a major component of the breast cancer stroma, molecular and phenotypic heterogeneity of CAFs in breast cancer is poorly understood. In this study, we investigated CAF heterogeneity in triple-negative breast cancer (TNBC) using a syngeneic mouse model, BALB/c-derived 4T1 mammary tumors. Using single-cell RNA sequencing (scRNA-seq), we identified six CAF subpopulations in 4T1 tumors including: 1) myofibroblastic CAFs, enriched for α-smooth muscle actin and several other contractile proteins; 2) ‘inflammatory’ CAFs with elevated expression of inflammatory cytokines; and 3) a CAF subpopulation expressing major histocompatibility complex (MHC) class II proteins that are generally expressed in antigen-presenting cells. Comparison of 4T1-derived CAFs to CAFs from pancreatic cancer revealed that these three CAF subpopulations exist in both tumor types. Interestingly, cells with inflammatory and MHC class II-expressing CAF profiles were also detected in normal breast/pancreas tissue, suggesting that these phenotypes are not tumor microenvironment-induced. This work enhances our understanding of CAF heterogeneity, and specifically targeting these CAF subpopulations could be an effective therapeutic approach for treating highly aggressive TNBCs.

Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis

2018 ◽  
Vol 24 (7) ◽  
pp. 986-993 ◽  
Author(s):  
Peter Savas ◽  
◽  
Balaji Virassamy ◽  
Chengzhong Ye ◽  
Agus Salim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Single Cell ◽  
Single Cell Profiling ◽  
Memory Subset

scholarly journals Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

2014 ◽  
Vol 60 (1) ◽  
pp. 233-242 ◽  
Author(s):  
Yaojun Li ◽  
Yueguo Li ◽  
Tao Chen ◽  
Anna S Kuklina ◽  
Paul Bernard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ex Vivo ◽  
Human Cell Line ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Orthotopic Implantation ◽  
Peptide Cleavage ◽  
Clinical Patient ◽  
Tumor Tissues ◽  
Carboxypeptidase N

Abstract BACKGROUND Carboxypeptidase N (CPN) is important in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. We investigated whether circulating peptides specifically cleaved by CPN in the tumor microenvironment can be stage-specific indicators of breast cancer. METHODS CPN activity was measured using an ex vivo peptide cleavage assay by incubating synthesized C3f peptide (His6-C3f_S1304-R1320-His6) in interstitial fluids of breast tumors and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. The nature and extent of peptide cleavage by CPN was investigated by fragment profiling using nanopore fractionation and mass spectrometry. The fragment profiles in interstitial fluid correlated with concentrations of CPN-catalyzed peptides in blood samples taken from the tumor-bearing mice, healthy women, and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting. RESULTS We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, CPN was clearly increased in tumor tissues compared with normal breast tissue, whereas corresponding CPN abundance in blood remained constant. Concentrations of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n = 8) at 2 weeks after orthotopic implantation. Six homologous peptides displayed significantly higher expression in the patients' plasma as early as the first pathologic stage of breast cancer. CONCLUSIONS Circulating CPN-catalyzed peptide concentrations reflect the CPN activity in tumors. These biomarkers show strong potential for the noninvasive and early diagnosis of breast cancer.

scholarly journals Labeling as a method of routine monitoring of tumor response to therapy

2021 ◽  
Vol 4 (1) ◽  
pp. 45-51
Author(s):  
T.A. Kravchun ◽  
A.A. Samusieva ◽  
V.V. Zaichuk
Keyword(s):  
Breast Cancer ◽  
Surgical Treatment ◽  
Literature Review ◽  
Tumor Response ◽  
Response To Therapy ◽  
Tumor Control ◽  
Tumor Site ◽  
Routine Monitoring ◽  
Complex Therapy

Surgical treatment is still one of the main methods of complex therapy of breast cancer. Due to the widespread use of non-adjuvant antitumor treatment, the issue of routine tumor labeling is becoming increasingly important. The purpose of labeling is to improve the quality of tumor control after neoadjuvant therapy and adequate surgical treatment. In this literature review, we will consider the methods for labeling to visualize a tumor site.

scholarly journals Single-Cell Profiling to Explore Immunological Heterogeneity of Tumor Microenvironment in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao Yuan ◽  
Jinxi Wang ◽  
Yixuan Huang ◽  
Dangang Shangguan ◽  
Peng Zhang
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Immune Cells ◽  
Critical Role ◽  
Therapy Resistance ◽  
Spatial Profiling ◽  
Wide Range ◽  
Single Cell Profiling ◽  
Immunological Heterogeneity

Immune infiltrates in the tumor microenvironment (TME) of breast cancer (BRCA) have been shown to play a critical role in tumorigenesis, progression, invasion, and therapy resistance, and thereby will affect the clinical outcomes of BRCA patients. However, a wide range of intratumoral heterogeneity shaped by the tumor cells and immune cells in the surrounding microenvironment is a major obstacle in understanding and treating BRCA. Recent progress in single-cell technologies such as single-cell RNA sequencing (scRNA-seq), mass cytometry, and digital spatial profiling has enabled the detailed characterization of intratumoral immune cells and vastly improved our understanding of less-defined cell subsets in the tumor immune environment. By measuring transcriptomes or proteomics at the single-cell level, it provides an unprecedented view of the cellular architecture consist of phenotypical and functional diversities of tumor-infiltrating immune cells. In this review, we focus on landmark studies of single-cell profiling of immunological heterogeneity in the TME, and discuss its clinical applications, translational outlook, and limitations in breast cancer studies.

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