352 Evaluation of EGFR, VEGFR2, IGF-1R and HIF-1a Expression and Their Prognostic Value in Iranian Triple-negative Breast Cancer Patients

Mehdizadeh, Reza; Najafi, Shamsoulmolouk; Jahanzad, Issa

doi:10.1016/s0959-8049(12)70418-5

Cited by 2 publications

(1 citation statement)

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“…The development of resistance to chemotherapy is a major problem in cancer treatment, including for TNBCs [ 11 , 12 , 13 ]. Many studies focus on overcoming resistance by introducing a combination of multiple cytotoxic drugs, targeted therapies, and immunotherapies [ 14 , 15 , 16 , 17 , 18 ]. High intra-tumor heterogeneity promotes the evolution of resistance that may be further modulated by active immune responses.…”

Section: Introductionmentioning

confidence: 99%

Dormant Tumor Cell Vaccination: A Mathematical Model of Immunological Dormancy in Triple-Negative Breast Cancer

Mehdizadeh

Shariatpanahi

Goliaei

et al. 2021

Cancers

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Triple-negative breast cancer (TNBC) is a molecular subtype of breast malignancy with a poor clinical prognosis. There is growing evidence that some chemotherapeutic agents induce an adaptive anti-tumor immune response. This reaction has been proposed to maintain the equilibrium phase of the immunoediting process and to control tumor growth by immunological cancer dormancy. We recently reported a model of immunological breast cancer dormancy based on the murine 4T1 TNBC model. Treatment of 4T1 cells in vitro with high-dose chemotherapy activated the type I interferon (type I IFN) signaling pathway, causing a switch from immunosuppressive to cytotoxic T lymphocyte-dependent immune response in vivo, resulting in sustained dormancy. Here, we developed a deterministic mathematical model based on the assumption that two cell subpopulations exist within the treated tumor: one population with high type I IFN signaling and immunogenicity and lower growth rate; the other population with low type I IFN signaling and immunogenicity and higher growth rate. The model reproduced cancer dormancy, elimination, and immune-escape in agreement with our previously reported experimental data. It predicted that the injection of dormant tumor cells with active type I IFN signaling results in complete growth control of the aggressive parental cancer cells injected at a later time point, but also of an already established aggressive tumor. Taken together, our results indicate that a dormant cell population can suppress the growth of an aggressive counterpart by eliciting a cytotoxic T lymphocyte-dependent immune response.

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