Immune parameters affecting the efficacy of chemotherapeutic regimens. Nature reviews

INSERM U1015, Institut Gustave Roussy, 39 rue Camille Desmoulins, F-94805 Villejuif, France.
Nature Reviews Clinical Oncology (Impact Factor: 14.18). 03/2011; 8(3):151-60. DOI: 10.1038/nrclinonc.2010.223
Source: PubMed


The outcome of chemotherapy can be influenced by the host immune system at multiple levels. Chemotherapy can kill cancer cells by causing them to elicit an immune response or alternatively, by increasing their susceptibility to immune attack. In addition, chemotherapy can stimulate anticancer immune effectors either in a direct fashion or by subverting immunosuppressive mechanisms. Beyond cancer-cell-intrinsic factors that determine the cytotoxic or cytostatic response, as well as the potential immunogenicity of tumor cells, the functional state of the host immune system has a major prognostic and predictive impact on the fate of cancer patients treated with conventional or targeted chemotherapies. In this Review, we surmise that immune-relevant biomarkers may guide personalized therapeutic interventions including compensatory measures to restore or improve anticancer immune responses.

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    • "It is known that severe lymphopenia (<1000 cells/μl) negatively affects the chemotherapy response. A collection of mouse cancers, including CT26 colon cancer, MCA205 fibrosarcomas, TSA cell line breast cancers, GOS cell line osteosarcomas, and EL4 thymomas, respond to chemotherapy with doxorubicin and oxaliplatin much more efficiently when they are implanted in syngenic immune-competent mice than in immunedeficient hosts, i.e., nude mice [51]. This is in line with clinical studies revealing that interferon-gamma (IFN-γ)–producing CD8 + T-LYM are potent cancer immune effectors. "
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    ABSTRACT: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) participate in pathological tissue damage. Mitochondrial manganese superoxide dismutase (MnSOD) normally keeps ROS and RNS in check. During development of mangafodipir (MnDPDP) as a magnetic resonance imaging (MRI) contrast agent, it was discovered that MnDPDP and its metabolite manganese pyridoxyl ethyldiamine (MnPLED) possessed SOD mimetic activity. MnDPDP has been tested as a chemotherapy adjunct in cancer patients and as an adjunct to percutaneous coronary intervention in patients with myocardial infarctions, with promising results. Whereas MRI contrast depends on release of Mn2+, the SOD mimetic activity depends on Mn2+ that remains bound to DPDP or PLED. Calmangafodipir [Ca4Mn(DPDP)5] is stabilized with respect to Mn2+ and has superior therapeutic activity. Ca4Mn(DPDP)5 is presently being explored as a chemotherapy adjunct in a clinical multicenter Phase II study in patients with metastatic colorectal cancer.
    Full-text · Article · Nov 2014 · Drug Discovery Today
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    • "The role of P2X7 purinergic receptors in anticancer immune response and response to chemotherapy is not clear. Chemotherapy fails in the absence of the purinergic receptor in breast and colon cancer [17], but loss-of-function alleles in P2X7 do not affect overall survival in NSCLC patients, irrespective of the administration and type of chemotherapy [18]. A possible explanation for this difference is that bronchial carcinomas may be subjected to a less vigorous immunosurveillance than tumors located in other organs, such as the mammary gland or the colic mucosa. "
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    ABSTRACT: Background P2X7, a purinergic receptor, plays important roles in inflammatory diseases, but recently its expression has been found in several tumors, suggesting a potential role as a cancer cell biomarker. Moreover, the relative amount of P2X7 varies among human individuals due to numerous single nucleotide polymorphisms resulting in either a loss- or gain-of-function; the P2X7 gene is highly polymorphic, and polymorphisms in the promoter or coding region may modify its expression or function. A polymorphism in exon 13 of the P2X7 receptor gene at the +1513 position (Glu496Ala substitution, corresponding to SNP rs3751143) has been shown to eradicate the function of this receptor and has been correlated with histological variants and clinical parameters in thyroid cancer. Until now, no data regarding P2X7 expression and polymorphisms in lung cancer have been published; based on these premises, we decided to evaluate the impact of the P2X7 expression and polymorphisms in ninety-seven cases of non-small cell lung cancer (NSCLC). Results No significant difference in the genotype frequency of the A1513C polymorphism was found between the two histological variants of NSCLC, adenocarcinoma and squamous cell carcinoma, and no statistically significant associations were observed between P2X7 protein expression and the main clinico-pathological characteristics of the NSCLC patients. Conclusions Based on our results, P2X7 expression and polymorphisms seem to have no potential impact in patients with non-small cell lung cancer; however, further studies will surely provide deeper insights regarding the role of this receptor at the clinical level in NSCLC.
    Full-text · Article · Sep 2014 · Journal of Negative Results in BioMedicine
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    • "Colorectal cancer (CRC) is one of the most common cancers and a major cause of death due to cancer worldwide. The functional state of the host immune system has a major prognostic and predictive impact on the fate of cancer patients treated with conventional or targeted chemotherapies [1]. "
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    ABSTRACT: Chemotherapy is one of most significant therapeutic approaches to cancer. Immune system functional state is considered a major prognostic and predictive impact on the success of chemotherapy and it has an important role on patients' psychoemotional state and quality of life. In Chinese medicine, chemotherapy is understood as "toxic cold" that may induce a progressive hypofunctional state of immune system, thus compromising the fast recovery of immunity during chemotherapy. In this study, we performed a standardized acupuncture and moxibustion protocol to enhance immunity in cancer patients undergoing chemotherapy and to assess if the improvement of immunity status correlates with a better psychoemotional state and quality of life.
    Full-text · Article · Jul 2014 · Evidence-based Complementary and Alternative Medicine
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