Regulation of Immunity in Breast Cancer

Edechi, Chidalu A.; Ikeogu, Nnamdi; Uzonna, Jude E.; Myal, Yvonne

doi:10.3390/cancers11081080

Cited by 55 publications

(44 citation statements)

References 119 publications

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“…The predominance of Th2 over Th1 lymphocytes has been shown previously to associate with breast cancer development and progression [22,23]. Th1 cells secrete interferon-γ (IFN-γ), Interleukin-2 (IL-2), and tumor necrosis factor (TNF-α) that result in an anti-cancer tumor immune microenvironment [24]. Conversely, Th2 cells demonstrate pro-cancer function via the secretion of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) [25].…”

Section: Introductionmentioning

confidence: 99%

High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer

Tokumaru

Asaoka

Oshi

et al. 2020

IJMS

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microRNA-143 (miR-143) is a well-known tumor suppressive microRNA that exhibits anti-tumoral function by targeting KRAS signaling pathways in various malignancies. We hypothesized that miR-143 suppresses breast cancer progression by targeting KRAS and its effector molecules. We further hypothesized that high expression of miR-143 is associated with a favorable tumor immune microenvironment of estrogen receptor (ER)-positive breast cancer patients which result in improved survival. Two major publicly available breast cancer cohorts; The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used. The miR-143 high expression group was associated with increased infiltration of anti-cancer immune cells and decreased pro-cancer immune cells, as well as enrichment of the genes relating to T helper (Th1) cells resulting in improved overall survival (OS) in ER-positive breast cancer patients. To the best of our knowledge, this is the first study to demonstrate that high expression of miR-143 in cancer cells associates with a favorable tumor immune microenvironment, upregulation of anti-cancer immune cells, and suppression of the pro-cancer immune cells, associating with better survival of the breast cancer patients.

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Section: Introductionmentioning

confidence: 99%

High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer

Tokumaru

Asaoka

Oshi

et al. 2020

IJMS

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“…Immunotherapy strategies are becoming the newly promising therapeutic options. [46][47][48] Therefore, we choose 4T1 breast tumor as an animal model for stage IV human breast cancer to investigate the anti-tumor efficacy of our therapeutic cancer vaccine. 49,50 Because of the immune escape mechanisms such as immunosuppressive environment and over-expression of inhibitory molecules, all lead to the failure of immunotherapy during cancer progression, cancer vaccines are unlikely to become a monotherapy of cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells</p>

Huang¹,

Zhao²,

Wei³

et al. 2020

IJN

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Background and Aim: We have previously identified ubiquitinated proteins (UPs) from tumor cell lysates as a promising vaccine for cancer immunotherapy in different mouse tumor models. In this study, we aimed at developing a highly efficient therapeutic adjuvant built-in nanovaccine (α-Al 2 O 3-UPs) by a simple method, in which UPs from tumor cells could be efficiently and conveniently enriched by α-Al 2 O 3 nanoparticles covalently coupled with Vx3 proteins (α-Al 2 O 3-CONH-Vx3). Methods: The α-Al 2 O 3 nanoparticles were modified with 4-hydroxybenzoic acid followed by coupling with ubiquitin-binding protein Vx3. It was then used to enrich UPs from 4T1 cell lysate. The stability and the efficiency for the UPs enrichment of α-Al 2 O 3-CONH-Vx3 were examined. The ability of α-Al 2 O 3-UPs to activate DCs was examined in vitro subsequently. The splenocytes from the vaccinated mice were re-stimulated with inactivated tumor cells, and the IFN-γ secretion was detected by ELISA and flow cytometry. Moreover, the therapeutic efficacy of α-Al 2 O 3-UPs, alone and in combination with chemotherapy, was examined in 4T1 tumor-bearing mice. Results: Our results showed that α-Al 2 O 3-UPs were successfully synthesized and abundant UPs from tumor cell lysate were enriched by the new method. In vitro study showed that compared to the physical mixture of α-Al 2 O 3 nanoparticles and UPs (α-Al 2 O 3 +UPs), α-Al 2 O 3-UPs stimulation resulted in higher upregulations of CD80, CD86, MHC class I, and MHC class II on DCs, indicating the higher ability of DC activation. Moreover, α-Al 2 O 3-UPs elicited a more effective immune response in mice, demonstrated by higher IFN-γ secretion than α-Al 2 O 3 +UPs. Furthermore, α-Al 2 O 3-UPs also exhibited a more potent effect on tumor growth inhibition and survival prolongation in 4T1 tumor-bearing mice. Notably, when in combination with low dose chemotherapy, the anti-tumor effect was further enhanced, rather than using α-Al 2 O 3-UPs alone. Conclusion: This study presents an adjuvant built-in nanovaccine generated by a new simple method that can be potentially applied to cancer immunotherapy and lays the experimental foundation for future clinical application.

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“…Similar to certain components of the immune system that are known to participate in the prevention and elimination of cancer, other components of the immune system can promote cancer progression and metastasis. 28 Myeloidderived suppressor cells (MDSC), alternatively activated (M2) macrophages, and regulatory T cells have been shown to secrete factors that suppress anti-tumour immune responses. 29 MDSC secrete TGF-β and vascular endothelial growth factor (VEGF) which stimulate EMT and angiogenesis, facilitating tumour growth and metastasis.…”

Section: Epithelial-mesenchymal Transitionmentioning

confidence: 99%

“…These include the use of tumour antigen-specific antibodies and adoptive transfer of activated immune cells, such as natural killer cells, dendritic cells, and T cells. 28 A recent study was the first to demonstrate no signs of cancer in a patient with metastatic breast cancer following treatment by adoptive transfer of activated patient-derived tumour-specific T cells. 63 Pembrolizumab, an anti-PD1 antibody, has been shown to be effective for patients with metastatic TNBC in clinical trials.…”

Section: Immunotherapy: Homing In On Our Immune Responsementioning

confidence: 99%

Metastasis: A Bane of Breast Cancer Therapy

2020

EMJ

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The underlying mechanisms of metastasis in patients with breast cancer is still poorly understood. Approximately 6% of patients with breast cancer present with metastasis at the time of diagnosis. Metastatic breast cancer is difficult to treat and patients with breast cancer with distant metastasis have a significantly lower 5-year survival rate compared to patients with localised breast cancer (27% and 99%, respectively). During breast cancer progression, tumour cells first metastasise to nearby draining lymph nodes and then to distant organs, primarily bone, lungs, liver, and brain. In this brief review, the authors discuss breast cancer metastasis, the role of epithelial–mesenchymal transition and the contributions of the immune system to the metastatic process. The authors also briefly discuss whether there is any relationship between tumour size and metastatic potential, and recent advances in treatment for metastatic breast cancer. The studies highlighted suggest that immunotherapy may play a more significant role in future patient care for metastatic breast cancer.

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Regulation of Immunity in Breast Cancer

Cited by 55 publications

References 119 publications

High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer

High Expression of microRNA-143 is Associated with Favorable Tumor Immune Microenvironment and Better Survival in Estrogen Receptor Positive Breast Cancer

<p>Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells</p>

Metastasis: A Bane of Breast Cancer Therapy

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