Abstract PO002: APOBEC mutagenesis as a driver of tumor evolution by promoting tumor recurrence and modulating tumor-immune system interactions in a syngeneic murine model of breast cancer

Abstract The goal of this study is to develop an integrated, mathematical–experimental approach for understanding the interactions between the immune system and the effects of trastuzumab on breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2+). A system of coupled, ordinary differential equations was constructed to describe the temporal changes in tumour growth, along with intratumoural changes in the immune response, vascularity, necrosis and hypoxia. The mathematical model is calibrated with serially acquired experimental data of tumour volume, vascularity, necrosis and hypoxia obtained from either imaging or histology from a murine model of HER2+ breast cancer. Sensitivity analysis shows that model components are sensitive for 12 of 13 parameters, but accounting for uncertainty in the parameter values, model simulations still agree with the experimental data. Given theinitial conditions, the mathematical model predicts an increase in the immune infiltrates over time in the treated animals. Immunofluorescent staining results are presented that validate this prediction by showing an increased co-staining of CD11c and F4/80 (proteins expressed by dendritic cells and/or macrophages) in the total tissue for the treated tumours compared to the controls ($p < 0.03$). We posit that the proposed mathematical–experimental approach can be used to elucidate driving interactions between the trastuzumab-induced responses in the tumour and the immune system that drive the stabilization of vasculature while simultaneously decreasing tumour growth—conclusions revealed by the mathematical model that were not deducible from the experimental data alone.

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Surface modification engineering of two-dimensional titanium carbide for efficient synergistic multitherapy of breast cancer

Journal of Materials Chemistry B ◽

10.1039/d0tb01084g ◽

2020 ◽

Vol 8 (30) ◽

pp. 6402-6417 ◽

Cited By ~ 1

Author(s):

Lei Bai ◽

Wenhui Yi ◽

Taiyang Sun ◽

Yilong Tian ◽

Ping Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Surface Modification ◽

Immune System ◽

Titanium Carbide ◽

Drug Delivery System ◽

Delivery System ◽

Tumor Recurrence ◽

Two Dimensional ◽

System P

A nanocomposite drug delivery system (Ti3C2@Met@CP) can be used for the synergistic treatment of tumors through photothermal/photodynamic/chemotherapy and can also inhibit tumor recurrence and metastasis by activating the immune system.

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The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

Breast Disease ◽

10.3233/bd-219002 ◽

2021 ◽

pp. 1-6

Author(s):

Upik A. Miskad ◽

Rizki A. Rifai ◽

Rina Masadah ◽

Berti Nelwan ◽

Djumadi Ahmad ◽

...

Keyword(s):

Breast Cancer ◽

Immune System ◽

Breast Carcinoma ◽

Neoadjuvant Chemotherapy ◽

Predictive Value ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Invasive Breast Carcinoma ◽

Study Results ◽

Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

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Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Viruses ◽

10.3390/v13061128 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1128

Author(s):

Amy Kwan ◽

Natalie Winder ◽

Munitta Muthana

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Cell Death ◽

Immune System ◽

Menopausal Status ◽

Oncolytic Virotherapy ◽

Immunogenic Cell Death ◽

Tumour Type ◽

Common Cancer ◽

Direct Cell

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

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Immunotherapy: New insights in breast cancer treatment

Human Antibodies ◽

10.3233/hab-210443 ◽

2021 ◽

pp. 1-10

Author(s):

Bader Alshehri

Keyword(s):

Breast Cancer ◽

Immune Response ◽

Immune System ◽

Cancer Treatment ◽

Immune Evasion ◽

Breast Tumor ◽

Parp Inhibitor ◽

Breast Cancer Treatment ◽

New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

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The Emerging Role of Extracellular Vesicles in Endocrine Resistant Breast Cancer

Cancers ◽

10.3390/cancers13051160 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1160

Author(s):

Giusi La Camera ◽

Luca Gelsomino ◽

Amanda Caruso ◽

Salvatore Panza ◽

Ines Barone ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Extracellular Vesicles ◽

Molecular Mechanisms ◽

Endocrine Resistance ◽

Disease Recurrence ◽

Estrogen Receptor Α ◽

Research Area ◽

Tumor Evolution

Breast cancer is the most common solid malignancy diagnosed in females worldwide, and approximately 70% of these tumors express estrogen receptor α (ERα), the main biomarker of endocrine therapy. Unfortunately, despite the use of long-term anti-hormone adjuvant treatment, which has significantly reduced patient mortality, resistance to the endocrine treatments often develops, leading to disease recurrence and limiting clinical benefits. Emerging evidence indicates that extracellular vesicles (EVs), nanosized particles that are released by all cell types and responsible for local and systemic intercellular communications, might represent a newly identified mechanism underlying endocrine resistance. Unraveling the role of EVs, released by transformed cells during the tumor evolution under endocrine therapy, is still an open question in the cancer research area and the molecular mechanisms involved should be better defined to discover alternative therapeutic approaches to overcome resistance. In this review, we will provide an overview of recent findings on the involvement of EVs in sustaining hormonal resistance in breast cancer and discuss opportunities for their potential use as biomarkers to monitor the therapeutic response and disease progression.

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