Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors post-chemotherapy

ABSTRACT: Analysis of MCA205 tumors developed in C57bl/6 mice on day 2, 7 and 10 after intratumoral treatment with doxorubicin (DX) or PBS solvent. DX triggers the immunogenicity of dying tumor cell and activates anti-tumor immunity. Results provided insight into molecular basis of DX induced immune response. C57bl/6 mice bearing palpable MCA205 fibrosarcoma tumors (25-45mm2) were treated with DX or PBS intratumorally and tumors were recovered 2, 7 or 10 days post treatment. DX treated samples on day 7 were also divided into responder and non responder groups according to tumor shrinkage.

ORGANISM(S): Mus musculus

SUBMITTER: Joachim Schultze

PROVIDER: E-GEOD-46275 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy.

Ma Yuting Y Mattarollo Stephen R SR Adjemian Sandy S Yang Heng H Aymeric Laetitia L Hannani Dalil D Portela Catani João Paulo JP Duret Helene H Teng Michele W L MW Kepp Oliver O Wang Yidan Y Sistigu Antonella A Schultze Joachim L JL Stoll Gautier G Galluzzi Lorenzo L Zitvogel Laurence L Smyth Mark J MJ Kroemer Guido G

Cancer research 20131203 2

The therapeutic efficacy of anthracyclines relies, at least partially, on the induction of a dendritic cell- and T-lymphocyte-dependent anticancer immune response. Here, we show that anthracycline-based chemotherapy promotes the recruitment of functional CD11b(+)CD11c(+)Ly6C(high)Ly6G(-)MHCII(+) dendritic cell-like antigen-presenting cells (APC) into the tumor bed, but not into lymphoid organs. Accordingly, draining lymph nodes turned out to be dispensable for the proliferation of tumor antigen- ...[more]

PMID: 24302580

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Project description:The majority of human melanomas bears BRAF mutations and thus is treated with inhibitors of BRAF, such as vemurafenib. While patients with BRAF mutations often demonstrate an initial dramatic response to vemurafenib, relapse is extremely common. Thus, novel agents are needed for the treatment of these aggressive melanomas. Honokiol is a small molecule compound derived from Magnolia grandiflora that has activity against solid tumors and hematopoietic neoplasms. In order to increase the lipophilicity of honokiol, we have synthesized honokiol DCA, the dichloroacetate ester of honokiol. In addition, we synthesized a novel fluorinated honokiol analog, bis-trifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro). Both compounds exhibited activity against A375 melanoma in vivo, but honokiol DCA was more active. Gene arrays comparing treated with vehicle control tumors demonstrated induction of the respiratory enzyme succinate dehydrogenase B (SDHB) by treatment, suggesting that our honokiol analogs induce respiration in vivo. We then examined its effect against a pair of melanomas, LM36 and LM36R, in which LM36R differs from LM36 in that LM36R has acquired vemurafenib resistance. Honokiol DCA demonstrated in vivo activity against LM36R (vemurafenib resistant) but not against parental LM36. Honokiol DCA and hexafluoro inhibited the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Honokiol DCA may act in vemurafenib resistant melanomas to increase both respiration and reactive oxygen generation, leading to activity against aggressive melanoma in vivo. Tumors from animals treated with control vehicle, honokiol DCA, and hexafluoro were harvested and snapped-frozen in liquid nitrogen until RNA Extraction. RNA extraction was performed according to the Qiagen RNeasy kit. RNA samples were then submitted to Emory Universityâs Intergrated Genomics Core for RNA quality analysis and gene expression assay. Gene expression analysis was performed using an Illumina HumanHT-12 v3 Expression Bead Chip and Gene Expression Module of Illuminaâs GenomeStudio Software package (v2011.1, Illumina).

Dataset Information

CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors post-chemotherapy

Publications

CCL2/CCR2-dependent recruitment of functional antigen-presenting cells into tumors upon chemotherapy.

Similar Datasets

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