New insights into metronomic chemotherapy-induced immunoregulation

Antitumor activity of mHSP65-TTL enhanced by administration of low dose cyclophosphamide in pancreatic cancer-bearing mice

“…Treg cells were found expanded in the peripheral blood and within the tumors of patients with breast, lung, liver, ovarian, pancreatic and gastric cancers [57][58][59][60] and [61], correlating with a poor prognosis [62][63][64] and [65]. The data suggest that CY could be used with cancer vaccines to eliminate Treg cells in tumor patients to reach a successful therapy [66], which could be supported by the evidences from both of the animal studies and clinical trials. A single injection of low dose CY at 30 mg/kg strongly depleted Treg cells by day 7 after the treatment in rats [67].…”

Optimal Control of Cancer Treatments: Mathematical Models for the Tumor Microenvironment

“…Metronomic chemotherapy is the almost uninterrupted, low-dose administration of chemotherapy. It has been shown to have both anti-angiogenic and immune stimulatory effects in clinical trials [2,20]. Clearly, therefore an adequate model needs to incorporate both of these components of the microenvironment.…”

“…High dose, MTD-style (maximum tolerated dose) treatments generally suppress all three compartments considered so far, the tumor, its vasculature and the immune system. Low dose treatments, however, in medical trials have been shown to have both anti-angiogenic and immune stimulatory effects [9,19,20,27]. Metronomic chemotherapy [2,3,46] tries to take advantage of these features by administering chemotherapy at a low dose in a regular manner, almost without interruptions.…”

“…The interactions between these treatment modalities are complex and have become the topic of intense medical research, e.g., [6,[19][20][21][22]27]. In this context, mathematical modeling and analysis can be useful by providing a framework for cancer progression and its response to various treatment options.…”

CpG-1826 immunotherapy potentiates chemotherapeutic and anti-tumor immune responses to metronomic cyclophosphamide in a preclinical glioma model

“…CPA depletes immune suppressive myeloid-derived suppressor cells and T regulatory cells, restores NK cell and T cell proliferation and cytotoxic activity, and promotes Th1 cytokine production [26,27]. Further, chemotherapy administered on a metronomic schedule [28,29] is increasingly recognized for its potential to induce unique immune-stimulatory responses [30–34]. Non-toxic doses of chemotherapeutic drugs may render tumor cells more immunogenic [35], highlighting the potential advantages of combining low dose chemotherapy with immunotherapy.…”