Recombinant Virus-Like Particles Presenting IL-33 Successfully Modify the Tumor Microenvironment and Facilitate Antitumor Immunity in a Model of Breast Cancer

2019 ◽  
Author(s):  
Xuejun Feng ◽  
Hongxian Liu ◽  
Xiaojie Chu ◽  
Pengyan Sun ◽  
Weiwei Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Recombinant Virus ◽  
Antitumor Immunity ◽  
Virus Like Particles

scholarly journals Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti–PD-1 for tumor abrogation

2018 ◽  
Vol 116 (4) ◽  
pp. 1361-1369 ◽  
Author(s):  
Irena Kaplanov ◽  
Yaron Carmi ◽  
Rachel Kornetsky ◽  
Avishai Shemesh ◽  
Galina V. Shurin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Antitumor Immunity ◽  
Inflammatory Monocytes ◽  
Mouse Breast Cancer ◽  
Low Levels ◽  
Early Tumor ◽  
4T1 Breast Cancer ◽  
Deficient Mice

Interleukin-1β (IL-1β) is abundant in the tumor microenvironment, where this cytokine can promote tumor growth, but also antitumor activities. We studied IL-1β during early tumor progression using a model of orthotopically introduced 4T1 breast cancer cells. Whereas there is tumor progression and spontaneous metastasis in wild-type (WT) mice, in IL-1β–deficient mice, tumors begin to grow but subsequently regress. This change is due to recruitment and differentiation of inflammatory monocytes in the tumor microenvironment. In WT mice, macrophages heavily infiltrate tumors, but in IL-1β–deficient mice, low levels of the chemokine CCL2 hamper recruitment of monocytes and, together with low levels of colony-stimulating factor-1 (CSF-1), inhibit their differentiation into macrophages. The low levels of macrophages in IL-1β–deficient mice result in a relatively high percentage of CD11b+dendritic cells (DCs) in the tumors. In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1β–deficient mice, IL-12 secretion by CD11b+DCs prevails and supports antitumor immunity. The antitumor immunity in IL-1β–deficient mice includes activated CD8+lymphocytes expressing IFN-γ, TNF-α, and granzyme B; these cells infiltrate tumors and induce regression. WT mice with 4T1 tumors were treated with either anti–IL-1β or anti–PD-1 Abs, each of which resulted in partial growth inhibition. However, treating mice first with anti–IL-1β Abs followed by anti–PD-1 Abs completely abrogated tumor progression. These data define microenvironmental IL-1β as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1β facilitates checkpoint inhibition.

scholarly journals Expression of membrane anchored cytokines and B7-1 alters tumor microenvironment and induces protective antitumor immunity in a murine breast cancer model

Vaccine ◽  
2013 ◽  
Vol 31 (20) ◽  
pp. 2449-2456 ◽  
Author(s):  
Erica N. Bozeman ◽  
Ashley Cimino-Mathews ◽  
Deepa K. Machiah ◽  
Jaina M. Patel ◽  
Arun Krishnamoorthy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Antitumor Immunity ◽  
Cancer Model ◽  
Breast Cancer Model

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

scholarly journals Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer

2020 ◽  
Vol 62 (1) ◽  
pp. 110-118
Author(s):  
Isabel Linares-Galiana ◽  
Miguel Angel Berenguer-Frances ◽  
Rut Cañas-Cortés ◽  
Monica Pujol-Canadell ◽  
Silvia Comas-Antón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Single Dose ◽  
Cancer Patients ◽  
Antitumor Immunity ◽  
Low Risk ◽  
Intraoperative Radiation Therapy ◽  
Breast Cancer Patients ◽  
Intraoperative Radiation ◽  
Risk Breast Cancer

Abstract A detailed understanding of the interactions and the best dose-fractionation scheme of radiation to maximize antitumor immunity have not been fully established. In this study, the effect on the host immune system of a single dose of 20 Gy through intraoperative radiation therapy (IORT) on the surgical bed in low-risk breast cancer patients undergoing conserving breast cancer has been assessed. Peripheral blood samples from 13 patients were collected preoperatively and at 48 h and 3 and 10 weeks after the administration of radiation. We performed a flow cytometry analysis for lymphocyte subpopulations, natural killer cells (NK), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs). We observed that the subpopulation of NK CD56+high CD16+ increased significantly at 3 weeks after IORT (0.30–0.42%, P < 0.001), while no changes were found in immunosuppressive profile, CD4+CD25+Foxp3+Helios+ Treg cells, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (Mo-MDSCs). A single dose of IORT may be an effective approach to improve antitumor immunity based on the increase in NK cells and the non-stimulation of immunosuppressive cells involved in immune escape. These findings support future combinations of IORT with immunotherapy, if they are confirmed in a large cohort of breast cancer patients.

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