scholarly journals Subclonal heterogeneity and evolution in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ioanna Mavrommati ◽  
Flora Johnson ◽  
Gloria V. Echeverria ◽  
Rachael Natrajan
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Therapy Resistance ◽  
Response To Therapy ◽  
Preclinical Models ◽  
Disease Evolution ◽  
Molecular Barcoding ◽  
Current Therapies ◽  
Single Cell Profiling ◽  
Transcriptomic Changes

AbstractSubclonal heterogeneity and evolution are characteristics of breast cancer that play a fundamental role in tumour development, progression and resistance to current therapies. In this review, we focus on the recent advances in understanding the epigenetic and transcriptomic changes that occur within breast cancer and their importance in terms of cancer development, progression and therapy resistance with a particular focus on alterations at the single-cell level. Furthermore, we highlight the utility of using single-cell tracing and molecular barcoding methodologies in preclinical models to assess disease evolution and response to therapy. We discuss how the integration of single-cell profiling from patient samples can be used in conjunction with results from preclinical models to untangle the complexities of this disease and identify biomarkers of disease progression, including measures of intra-tumour heterogeneity themselves, and how enhancing this understanding has the potential to uncover new targetable vulnerabilities in breast cancer.

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.

scholarly journals MutaSeq reveals the transcriptomic consequences of clonal evolution in acute myeloid leukemia

2018 ◽  
Author(s):  
Lars Velten ◽  
Benjamin A. Story ◽  
Pablo Hernandez-Malmierca ◽  
Jennifer Milbank ◽  
Malte Paulsen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Single Cell ◽  
Myeloid Leukemia ◽  
Clonal Evolution ◽  
Depth Profiling ◽  
Therapy Resistance ◽  
Leukemic Cells ◽  
Cancer Evolution ◽  
Transcriptomic Changes ◽  
Acute Myeloid

The step-wise acquisition of genetic abnormalities in cancer is thought to represent a major driver of disease initiation, relapse and therapy resistance. Acute myeloid leukemia (AML) represents a prime example of an aggressive cancer that develops in a multi-step manner from multipotent hematopoietic progenitors via pre-leukemic intermediates to leukemic cells. While bulk and single-cell genomics provide powerful tools to study the phylogenetics of cancer evolution, the specific transcriptomic changes induced by the accumulation of mutations remain largely unexplored. Here, we introduce MutaSeq, a combined single-cell genetic and transcriptomics platform for the identification of molecular consequences of cancer evolution. Through in-depth profiling of an AML patient, we demonstrate that MutaSeq is capable of: (1) fine-mapping clonal and developmental hierarchies (2) quantifying the ability of leukemic and pre-leukemic clones to give rise to mature lineages and (3) identifying surface markers and mRNA transcripts specific to pre-leukemic, leukemic, and residual healthy cells. The experimental and analytical approach presented here is broadly applicable to other types of cancer, and can help identify targets for eradicating both pre-cancerous and cancerous reservoirs of relapse.

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 Multiparametric Analysis of Longitudinal Quantitative MRI Data to Identify Distinct Tumor Habitats in Preclinical Models of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1682
Author(s):  
Anum K. Syed ◽  
Jennifer G. Whisenant ◽  
Stephanie L. Barnes ◽  
Anna G. Sorace ◽  
Thomas E. Yankeelov
Keyword(s):  
Breast Cancer ◽  
Tumor Volume ◽  
Response To Therapy ◽  
Quantitative Mri ◽  
Preclinical Models ◽  
Ki 67 ◽  
Contrast Enhanced ◽  
High Cellularity ◽  
Magnetic Resonance Imaging Mri ◽  
Positive Correlations

This study identifies physiological tumor habitats from quantitative magnetic resonance imaging (MRI) data and evaluates their alterations in response to therapy. Two models of breast cancer (BT-474 and MDA-MB-231) were imaged longitudinally with diffusion-weighted MRI and dynamic contrast-enhanced MRI to quantify tumor cellularity and vascularity, respectively, during treatment with trastuzumab or albumin-bound paclitaxel. Tumors were stained for anti-CD31, anti-Ki-67, and H&E. Imaging and histology data were clustered to identify tumor habitats and percent tumor volume (MRI) or area (histology) of each habitat was quantified. Histological habitats were correlated with MRI habitats. Clustering of both the MRI and histology data yielded three clusters: high-vascularity high-cellularity (HV-HC), low-vascularity high-cellularity (LV-HC), and low-vascularity low-cellularity (LV-LC). At day 4, BT-474 tumors treated with trastuzumab showed a decrease in LV-HC (p = 0.03) and increase in HV-HC (p = 0.03) percent tumor volume compared to control. MDA-MB-231 tumors treated with low-dose albumin-bound paclitaxel showed a longitudinal decrease in LV-HC percent tumor volume at day 3 (p = 0.01). Positive correlations were found between histological and imaging-derived habitats: HV-HC (BT-474: p = 0.03), LV-HC (MDA-MB-231: p = 0.04), LV-LC (BT-474: p = 0.04; MDA-MB-231: p < 0.01). Physiologically distinct tumor habitats associated with therapeutic response were identified with MRI and histology data in preclinical models of breast cancer.

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 Macrophage Biology and Mechanisms of Immune Suppression in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Anita K. Mehta ◽  
Sapana Kadel ◽  
Madeline G. Townsend ◽  
Madisson Oliwa ◽  
Jennifer L. Guerriero
Keyword(s):  
Breast Cancer ◽  
Tumor Immunity ◽  
Immune Suppression ◽  
Therapy Resistance ◽  
Adverse Outcomes ◽  
Phenotypic Characterization ◽  
Before And After ◽  
Current Therapies ◽  
Subset Diversity ◽  
Future Work

Macrophages are crucial innate immune cells that maintain tissue homeostasis and defend against pathogens; however, their infiltration into tumors has been associated with adverse outcomes. Tumor-associated macrophages (TAMs) represent a significant component of the inflammatory infiltrate in breast tumors, and extensive infiltration of TAMs has been linked to poor prognosis in breast cancer. Here, we detail how TAMs impede a productive tumor immunity cycle by limiting antigen presentation and reducing activation of cytotoxic T lymphocytes (CTLs) while simultaneously supporting tumor cell survival, angiogenesis, and metastasis. There is an urgent need to overcome TAM-mediated immune suppression for durable anti-tumor immunity in breast cancer. To date, failure to fully characterize TAM biology and classify multiple subsets has hindered advancement in therapeutic targeting. In this regard, the complexity of TAMs has recently taken center stage owing to their subset diversity and tightly regulated molecular and metabolic phenotypes. In this review, we reveal major gaps in our knowledge of the functional and phenotypic characterization of TAM subsets associated with breast cancer, before and after treatment. Future work to characterize TAM subsets, location, and crosstalk with neighboring cells will be critical to counteract TAM pro-tumor functions and to identify novel TAM-modulating strategies and combinations that are likely to enhance current therapies and overcome chemo- and immuno-therapy resistance.

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