Immunotherapy and chemotherapy — a practical partnership

Lake, Richard; Robinson, Bruce

doi:10.1038/nrc1613

Cited by 600 publications

(409 citation statements)

References 62 publications

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“…For example, some anticancer drugs increase the expression of death receptors, including FAS, TNF receptors and TNF-related apoptosis-inducing ligand receptors. 94 Other drugs trigger apoptosis by inducing release of cytochrome c from mitochondria. 94 The degree of TCD correlates with clinical outcome in several tumor settings.…”

Section: Effects On Tumor Cells and On Tumor Microenvironmentmentioning

confidence: 99%

“…94 Other drugs trigger apoptosis by inducing release of cytochrome c from mitochondria. 94 The degree of TCD correlates with clinical outcome in several tumor settings. 95,96 Some chemotherapeutics, including anthracyclines, oxaliplatin and CTX, are unique in their capacity to induce an immunogenic type of TCD, 21,97 thereby converting dying tumor cells into adjuvanted-endogenous vaccines.…”

Section: Effects On Tumor Cells and On Tumor Microenvironmentmentioning

confidence: 99%

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Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

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Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

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Section: Effects On Tumor Cells and On Tumor Microenvironmentmentioning

confidence: 99%

Section: Effects On Tumor Cells and On Tumor Microenvironmentmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

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“…Therefore, many efforts have been directed toward the development of immunotherapeutic approaches to enable the immune system to respond specifically against cancer. 20,89 Dendritic cells have different sensitivities to conventional cytotoxic agents. In this aspect, it was reported that PTX and other chemotherapeutic agents could up-regulate DC functions in vitro.…”

Section: Immunomodulatory Effects Of Ultra-low Concentrations Of Chemmentioning

confidence: 99%

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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“…Conversely, TLR-targeted therapy may enhance subsequent responses to chemotherapy. Such combinations have been explored in a number of preclinical studies, sometimes with promising results (Lake and Robinson, 2005;Bourquin et al, 2006;Shi et al, 2007). For example, Shi et al (2007) demonstrated enhanced chemo-sensitivity of chronic lymphocytic leukemia cells after tolerizing treatment with the TLR7 agonist, S28690.…”

Section: Tlr Ligands In Cancer Immunotherapymentioning

confidence: 99%

Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer

Roses

Koski

et al. 2008

Oncogene

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Immunotherapy and chemotherapy — a practical partnership

Cited by 600 publications

References 62 publications

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

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

Radiation therapy and Toll-like receptor signaling: implications for the treatment of cancer

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