scholarly journals Aberrant glycolysis associates with inflammatory tumour microenvironment and promotes metastasis in triple negative breast cancer

2019 ◽  
Vol 30 ◽  
pp. v5 ◽  
Author(s):  
C. Lin
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumour Microenvironment

scholarly journals Prognostic significance of PD-L1-positive cancer-associated fibroblasts in patients with triple-negative breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Katsuhiro Yoshikawa ◽  
Mitsuaki Ishida ◽  
Hirotsugu Yanai ◽  
Koji Tsuta ◽  
Mitsugu Sekimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Tumour Microenvironment ◽  
Clinicopathological Parameters ◽  
Cancer Associated Fibroblasts ◽  
Clinicopathological Significance

Abstract Background Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1. Methods Immunohistochemical staining (primary antibodies of 73–10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined. Results Thirty-four (55.7%) patients were positive for CAF PD-L1 (73–10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73–10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044–0.891; p = 0.035). Conclusions CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73–10 assay may be suitable for immunostaining CAF PD-L1.

scholarly journals Depletion of CD206+ tumour macrophages by mUNO targeted nanoconjugate inhibits tumourigenesis and dissemination in triple negative breast cancer

2021 ◽  
Author(s):  
Anni Lepland ◽  
Alessio Malfanti ◽  
Uku Haljasorg ◽  
Eliana Asciutto ◽  
Monica Pickholz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Foxp3 Expression ◽  
Tumour Microenvironment ◽  
Solid Tumours ◽  
Fluorescent Reporter

Abstract Chemotherapy is the standard of care for patients with triple negative breast cancer (TNBC), an aggressive breast cancer subtype with a poor prognosis. In many solid tumours, M2-skewed tumour-associated macrophages (TAMs) are known to promote progression, immunosuppression, relapse, and dissemination of the malignant disease. Although TAM depletion has been explored as an anticancer strategy, the currently available TAM depleting compounds suffer from poor efficacy and dose-limiting side effects. Here, we develop of a novel TAM-depleting agent that specifically targets CD206+ macrophages and show that it is efficacious as an anti-TNBC agent and well tolerated. This new TAM-depleting compound, called “OximUNO”, is a star-shaped polyglutamate decorated with the CD206-targeting peptide mUNO and carrying doxorubicin through a pH-responsive linker. In the orthotopic and experimental metastases of TNBC, fluorescent reporter mUNO-guided polyglutamate construct homed to CD206+ macrophages in the primary cancer lesions and at the sites of metastases. OximUNO displayed enhanced cytotoxicity towards primary M2 macrophages in vitro and exhibited no acute liver or kidney toxicity in vivo. In TNBC mouse models, OximUNO reduced the progression of primary breast cancer lesions and metastatic dissemination of malignant cells. Treatment with OximUNO had an immunomodulatory effect on the tumour microenvironment: besides reducing the number of CD206+ TAMs, it resulted in increased ratio of the CD8/FOXP3 expression. These studies suggest the potential utility of OximUNO based CD206+ TAM depletion strategies for the treatment of TNBC, and possibly, other types of solid tumours.

scholarly journals How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies

ESMO Open ◽  
2018 ◽  
Vol 3 (Suppl 1) ◽  
pp. e000357 ◽  
Author(s):  
Ji Hyun Park ◽  
Jin-Hee Ahn ◽  
Sung-Bae Kim
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Tumour Microenvironment ◽  
Therapeutic Benefit ◽  
Current Standard

Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the ‘BRCAness’ highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors. However, regardless of enriched chemosensitivity and immunogenicity, majority of patients with TNBC still suffer from dismal clinical outcomes including early relapse and metastatic spread. Therefore, efforts into more precise and personalised treatment are critical at this point. Accordingly, the advance of multiomics has revealed novel actionable targets including PI3K-Akt-mTOR and epidermal growth factor receptor signalling pathways, which might actively participate in modulating the chemosensitivity and immune system. Also, TNBC has long been considered a potential protagonist of immunotherapy in breast cancer, supported by abundant tumour-infiltrating lymphocytes and heterogeneous tumour microenvironment. Despite that, earlier studies showed somewhat unsatisfactory results of monotherapy with immune-checkpoint inhibitors, consistently durable responses in responders were noteworthy. Based on these results, further combinatorial trials either with other chemotherapy or targeted agents are underway. Incorporating immune-molecular targets into combination as well as refining the standard chemotherapy might be the key to unlock the future of TNBC. In this review, we share the current and upcoming treatment options of TNBC in the framework of scientific and clinical data, especially focusing on early stage of TNBC.

scholarly journals Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

2022 ◽  
Vol 11 ◽  
Author(s):  
Arutha Kulasinghe ◽  
James Monkman ◽  
Esha T. Shah ◽  
Nicholas Matigian ◽  
Mark N. Adams ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Differential Expression Analysis ◽  
Tumour Microenvironment ◽  
Chemotherapy Response ◽  
Prognostic Features ◽  
Chemotherapeutic Response ◽  
Er Alpha

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has few effective treatment options due to its lack of targetable hormone receptors. Whilst the degree of tumour infiltrating lymphocytes (TILs) has been shown to associate with therapy response and prognosis, deeper characterization of the molecular diversity that may mediate chemotherapeutic response is lacking. Here we applied targeted proteomic analysis of both chemotherapy sensitive and resistant TNBC tissue samples by the Nanostring GeoMx Digital Spatial Platform (DSP). By quantifying 68 targets in the tumour and tumour microenvironment (TME) compartments and performing differential expression analysis between responsive and non-responsive tumours, we show that increased ER-alpha expression and decreased 4-1BB and MART1 within the stromal compartments is associated with adjuvant chemotherapy response. Similarly, higher expression of GZMA, STING and fibronectin and lower levels of CD80 were associated with response within tumour compartments. Univariate overall-survival (OS) analysis of stromal proteins supported these findings, with ER-alpha expression (HR=0.19, p=0.0012) associated with better OS while MART1 expression (HR=2.3, p=0.035) was indicative of poorer OS. Proteins within tumour compartments consistent with longer OS included PD-L1 (HR=0.53, p=0.023), FOXP3 (HR=0.5, p=0.026), GITR (HR=0.51, p=0.036), SMA (HR=0.59, p=0.043), while EPCAM (HR=1.7, p=0.045), and CD95 (HR=4.9, p=0.046) expression were associated with shorter OS. Our data provides early insights into the levels of these markers in the TNBC tumour microenvironment, and their association with chemotherapeutic response and patient survival.

Identification of new therapeutic leads for triple negative breast cancer subtypes

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
AJ Robles ◽  
L Du ◽  
S Cai ◽  
RH Cichewicz ◽  
SL Mooberry
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes ◽  
Therapeutic Leads

Immediate and long-term results of the first line chemotherapy in patients with metastatic triple negative breast cancer. Final analysis of randomized study

2020 ◽  
pp. 75-80
Author(s):  
S.A. Lyalkin ◽  
◽  
L.A. Syvak ◽  
N.O. Verevkina ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Randomized Study ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Group 2 ◽  
Line Chemotherapy ◽  
Group 1

The objective: was to evaluate the efficacy of the first line chemotherapy in patients with metastatic triple negative breast cancer (TNBC). Materials and methods. Open randomized study was performed including 122 patients with metastatic TNBC. The efficacy and safety of the first line chemotherapy of regimens АТ (n=59) – group 1, patients received doxorubicine 60 мг/м2 and paclitaxel 175 мг/м2 and ТР (n=63) – group 2, patients received paclitaxel 175 мг/м2 and carboplatin AUC 5 were evaluated. Results. The median duration of response was 9.5 months (4.5–13.25 months) in patients received AT regimen and 8.5 months (4.7–12.25 months), in TP regimen; no statistically significant differences were observed, р=0.836. The median progression free survival was 7 months (95% CI 5–26 months) in group 1 and 7.5 months (95% CI 6–35 months) in group 2, p=0.85. Both chemotherapy regimens (AT and TP) had mild or moderate toxicity profiles (grade 1 or 2 in most patients). No significant difference in gastrointestinal toxicity was observed. The incidence of grade 3–4 neutropenia was higher in patients of group 2 (TP regimen): 42.8% versus 27% (р<0.05). Conclusions. Both regimens of chemotherapy (AT and TP) are appropriate to use in the first line setting in patients with metastatic TNBC. Key words: metastatic triple negative breast cancer, chemotherapy, progression free survival, chemotherapy toxicity.

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