Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

Veltman, Joris D.; Lambers, Margaretha; Nimwegen, Menno van; Jong, Sanne de; Hendriks, Rudi W.; Hoogsteden, Henk C.; Aerts, Joachim; Hegmans, Joost P.

doi:10.1155/2010/798467

Cited by 35 publications

(34 citation statements)

References 50 publications

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“…If the number of CTLs is insufficient, they should either be induced by immunotherapy and/or by decreasing the immunosuppressive environment. Preclinical studies by our group support the concept that modulating the immunosuppressive environment in combination with therapies that simultaneously stimulate effector cells has clinical potential (63,71).…”

Section: Future Perspectivesmentioning

confidence: 80%

Tumor-Specific Cytotoxic T Cells Are Crucial for Efficacy of Immunomodulatory Antibodies in Patients with Lung Cancer

2013

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There is growing evidence that activation of the immune system may be an effective treatment for patients with either small cell lung cancer or non-small cell lung cancer (NSCLC). Immunomodulatory antibodies directed against cytotoxic T cell-associated antigen 4 (CTLA-4/CD152) and programmed cell death ligand 1 (PDL1/ CD274) showed clinical efficacy in patients with lung cancer. The key immune cells responsible for antitumor activity are the CTLs. The presence of these tumor-directed CTLs, both in number and functionality, is a prerequisite for the immune system to attack cancer cells. Immunomodulatory agents attempt to increase the efficacy of CTL activity. Thus, the limited number of patients who benefit from immunomodulatory antibodies may be caused by either an inadequate number or the impairment of CTL activity by the hostile environment created by the tumor. In this review, we discuss tumor-induced impairment of CTLs and experimental treatments that can stimulate T-cell responses and optimize specific CTL function. We discuss 2 types of immune cells with known suppressive capacity on CTLs that are of pivotal importance in patients with lung cancer: regulatory T cells and myeloid-derived suppressor cells. Cancer Res; 73(8);

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Section: Future Perspectivesmentioning

confidence: 80%

Tumor-Specific Cytotoxic T Cells Are Crucial for Efficacy of Immunomodulatory Antibodies in Patients with Lung Cancer

2013

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“…Cyclophosphamide can more specifically target Treg cells, though this appears to be somewhat dependent on dosage and timing [60]. Low-dose cyclophosphamide induces beneficial immunomodulatory effects by preventing the induction of Treg cells, and as a consequence, releases effector T cells from immunosuppression [61]. Pemetrexed/cisplatin is the standard first line chemotherapy for malignant mesothelioma but until recently pemetrexed had not been tested for effect on Treg cells.…”

Section: Improved Survival Results From Treg Cell Depletionmentioning

confidence: 99%

The Role of Regulatory T Cells in Mesothelioma

Ireland

Beilharz

2012

Cancer Microenvironment

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Malignant mesothelioma (MM) appears to be responsive to immunotherapy. The lack of complete tumour cure as a result of many immunotherapies tested to date suggests that the immune response to MM is complex and multi-parametric. Regulatory T (Treg) cells are prevalent within murine and human mesotheliomas with their removal shown to result in tumour growth inhibition and the release of anti-tumour effector T cells from immunosuppression. The targeting of immune checkpoints as treatments for various solid tumours has recently shown promise in clinical settings. In addition, synergy between chemotherapy and immunotherapy has been demonstrated for many cancers, including mesothelioma. Here we demonstrate Treg cells as critical mediators of the anti-tumour immune response to MM and potential targets for anti-tumour immunotherapy; though the timing and dosage of Treg cell manipulating immunotherapies need to be optimised.

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“…65 These results suggest that the DC-based antitumor treatment of patients might be improved by simultaneous depletion of Tregs using a low dose of CTX. Moreover, this combination significantly improves the survival of tumor-bearing mice, when compared with DC vaccination or CTX alone.…”

Section: Effects Of Ctx On the Immune Response And Combination With Imentioning

confidence: 87%

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Nars

Kaneno

2012

Intl Journal of Cancer

104

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Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy.

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Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

Cited by 35 publications

References 50 publications

Tumor-Specific Cytotoxic T Cells Are Crucial for Efficacy of Immunomodulatory Antibodies in Patients with Lung Cancer

Tumor-Specific Cytotoxic T Cells Are Crucial for Efficacy of Immunomodulatory Antibodies in Patients with Lung Cancer

The Role of Regulatory T Cells in Mesothelioma

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

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