The Immune Microenvironment of Breast Cancer Progression

Tower, Helen; Ruppert, Meagan; Britt, Kara

doi:10.3390/cancers11091375

Cited by 83 publications

(85 citation statements)

References 105 publications

(129 reference statements)

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“…Macrophages, neutrophils, myeloid-derived suppressor cells (MDSCs), and T and B lymphocytes mainly contribute to the immune tumor infiltrate, which plays an integral role in the evolution of breast cancer [ 106 ]. For instance, MDSCs that are highly up-regulated in pathological conditions such as the chronic infections and cancer may exhibit a strong immunosuppressive activity [ 107 ].…”

Section: The Functional Interplay Between Fgf/fgfr Signaling and Bmentioning

confidence: 99%

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Santolla

Maggiolini

2020

Cancers

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One of the major challenges in the treatment of breast cancer is the heterogeneous nature of the disease. With multiple subtypes of breast cancer identified, there is an unmet clinical need for the development of therapies particularly for the less tractable subtypes. Several transduction mechanisms are involved in the progression of breast cancer, therefore making the assessment of the molecular landscape that characterizes each patient intricate. Over the last decade, numerous studies have focused on the development of tyrosine kinase inhibitors (TKIs) to target the main pathways dysregulated in breast cancer, however their effectiveness is often limited either by resistance to treatments or the appearance of adverse effects. In this context, the fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) system represents an emerging transduction pathway and therapeutic target to be fully investigated among the diverse anti-cancer settings in breast cancer. Here, we have recapitulated previous studies dealing with FGFR molecular aberrations, such as the gene amplification, point mutations, and chromosomal translocations that occur in breast cancer. Furthermore, alterations in the FGF/FGFR signaling across the different subtypes of breast cancer have been described. Next, we discussed the functional interplay between the FGF/FGFR axis and important components of the breast tumor microenvironment. Lastly, we pointed out the therapeutic usefulness of FGF/FGFR inhibitors, as revealed by preclinical and clinical models of breast cancer.

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Section: The Functional Interplay Between Fgf/fgfr Signaling and Bmentioning

confidence: 99%

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Santolla

Maggiolini

2020

Cancers

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“…Bearing in mind that specific reactivation of patients' immune system is one of the major goals to improve breast cancer treatment, though the mechanisms refraining the antitumor immune responses might be different from patient to patient, it is important to further develop immunotherapies that work in individual patients. The tumor immune microenvironment (TIME) has been widely studied in breast cancer, in order to find new personalized therapeutic strategies based on immune-modulators that could aid the standard chemotherapeutic options and improve breast cancer patients' survival ( 11 ). In order to screen novel therapies, the development of new platforms that reliably mimic tumor structures should be addressed.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a 3D Co-culture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies

et al. 2020

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3D cell culture including different cell types, such as immune cells, is a representative platform that mimics the tumor microenvironment. Here we disclose an easy-to-handle 3D co-culture protocol using a scaffold-free technique with the breast cancer cell line MDA-MB-231 and breast cancer patient-derived immune cells from peripheral blood. The method presented is simple, less time-consuming and less expensive when compared to other 3D techniques. Additionally, this is an optimized protocol for the establishment of a 3D system for this cell line, which is normally seen as challenging to spontaneously form spheroids. The addition of patient-derived immune cells to the cancer cells' spheroid allows the study of the crosstalk between both cell types, as well as the assessment of individual therapeutic approaches to intensify the antitumor immune response. In fact, with this model, we observed that patients' immune cells exhibit a wide range of antitumor responses and we further demonstrated that it is possible to manipulate the less effective ones with a canonical stimulus, as a proof-of-concept, in order to improve their ability to lower the viability of tumor cells. Therefore, this platform could be applied for a personalized immune-based drug screening, with results after a maximum of 10 days of culture, in order to develop more tailored breast cancer treatments and ameliorate patients' survival rate.

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“…Given that the presence and/or absence of immune cells in the TIME have been shown to influence the course of disease including invasiveness, metastasis and prognosis [19,20], we next determined the relationship between overall survival and the TIME content of each individual cell type within the LM22 signature set. The presence of high levels (> 25th percentile) of specific lymphocyte types, Naive B cells (p=0.0033) and CD8 T cells (p=0.0013), conferred a significantly better prognosis compared to patients with lower TIME content of these cells (Figure 1b).…”

Section: Time Features Are Predictive Of Prognosis In Primary Human Bmentioning

confidence: 99%

The Primary Tumor Immune Microenviornment Status Predicts the Response to Immunotherapy and Overall Survival in Breast Cancer

Moorthy

Quinn

2020

Preprint

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II.AbstractThe tumor immune microenvironment (TIME) of breast cancer is a known source of tumor heterogeneity and it has been increasingly recognized as having a role in the course of disease. In the present study, we used a computational approach to dissect the landscape of TIME states among TCGA breast cancer patients. Our central hypothesis is that the pre-existing TIME states represent a dimension which is informative about the prognosis and the response to immunotherapy. In order to test this hypothesis, we first classified breast cancer patients according to their primary TIME status. Next, we describe a TIME-based classification with prognostic value for overall survival among the TCGA patients. We further demonstrated that absolute quantification of mast cells, M0 macrophages, CD8 T cells and neutrophils were predictive of overall survival. In order to identify the TIME states which, predict response to immune checkpoint blockade, we performed a similar analysis of 11 different mouse models of primary invasive breast carcinoma that were subsequently treated with immune checkpoint inhibitor (ICI) therapy. These analyses revealed that the TIME content of M1 macrophages, monocytes and resting dendritic cells were predictive of sensitivity to ICI therapy. Taken together, these results indicate that (1) the landscape of human primary TIME states is diverse and can identify patients with more or less aggressive disease and (2) that pre-existing TIME states may be able to identify patients, of all molecular subtypes of breast cancer, who are good candidates for ICI therapy.

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The Immune Microenvironment of Breast Cancer Progression

Cited by 83 publications

References 105 publications

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives

Establishment of a 3D Co-culture With MDA-MB-231 Breast Cancer Cell Line and Patient-Derived Immune Cells for Application in the Development of Immunotherapies

The Primary Tumor Immune Microenviornment Status Predicts the Response to Immunotherapy and Overall Survival in Breast Cancer

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