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Modjtahedi N.,French Institute of Health and Medical Research | Modjtahedi N.,Institute Gustave Roussy Cancer Campus | Modjtahedi N.,University Paris - Sud | Hangen E.,French Institute of Health and Medical Research | And 8 more authors.
Cell Cycle | Year: 2015

Hypomorphic mutation of apoptosis-inducing factor (AIF) in the whole body or organ-specific knockout of AIF compromises the activity of respiratory chain complexes I and IV, as it confers resistance to obesity and diabetes induced by high-fat diet. The mitochondrial defect induced by AIF deficiency can be explained by reduced AIF-dependent mitochondrial import of CHCHD4, which in turn is required for optimal import and assembly of respiratory chain complexes. Here we show that, as compared to wild type control littermates, mice with a heterozygous knockout of CHCHD4 exhibit reduced weight gain when fed with a Western style high-fat diet. This finding suggests widespread metabolic epistasis among AIF and CHCHD4. Targeting either of these proteins or their functional interaction might constitute a novel strategy to combat obesity. © 2015 Taylor & Francis Group, LLC.


Stoll G.,University of Paris Descartes | Stoll G.,French Institute of Health and Medical Research | Stoll G.,University Pierre and Marie Curie | Zitvogel L.,Metabolomics and Cell Biology Platforms | And 6 more authors.
OncoImmunology | Year: 2016

Recently, we interrogated public microarray databases with regard to the expression patterns of metagenes corresponding to major immune cell subtypes present in malignant tumors. This analysis, which involved approximately 3,500 tumor samples, revealed organ-specific differences in the composition of the immune infiltrate as well as in the correlation among distinct cell-type specific metagenes, reflecting changes in the functional organization of the anticancer immune response. © 2016 Taylor & Francis Group, LLC.


Stoll G.,University of Paris Descartes | Stoll G.,French Institute of Health and Medical Research | Stoll G.,University Pierre and Marie Curie | Bindea G.,University of Paris Descartes | And 15 more authors.
Oncotarget | Year: 2015

Anticancer immunosurveillance is one of the major endogenous breaks of tumor progression. Here, we analyzed gene expression pattern indicative of the presence of distinct leukocyte subtypes within four cancer types (breast cancer, colorectal carcinoma, melanoma, and non-small cell lung cancer) and 20 different microarray datasets corresponding to a total of 3471 patients. Multiple metagenes reflecting the presence of such immune cell subtypes were highly reproducible across distinct cohorts. Nonetheless, there were sizable differences in the correlation patterns among such immune-relevant metagenes across distinct malignancies. The reproducibility of the correlations among immune-relevant metagenes was highest in breast cancer (followed by colorectal cancer, non-small cell lung cancer and melanoma), reflecting the fact that mammary carcinoma has an intrinsically better prognosis than the three other malignancies. Among breast cancer patients, we found that the expression of a lysosomal enzyme-related metagene centered around ASAH1 (which codes for N-acylsphingosine amidohydrolase-1, also called acid ceramidase) exhibited a higher correlation with multiple immune-relevant metagenes in patients that responded to neoadjuvant chemotherapy than in non-responders. Altogether, this meta-analysis revealed novel organ-specific features of the immune infiltrate in distinct cancer types, as well as a strategy for defining new prognostic biomarkers.


Calvo F.A.,Hospital General Universitario | Calvo F.A.,Complutense University of Madrid | Sole C.V.,Institute Gustave Roussy Cancer Campus | Rivera S.,Institute Gustave Roussy Cancer Campus | And 9 more authors.
Clinical and Translational Oncology | Year: 2014

Age is an important feature at the time of early breast cancer diagnosis. Radiotherapy is a mandatory component of treatment for breast-conserving strategies in early disease stages. Breast radiotherapy has rapidly evolved in the last 20 years. A tendency to less treatment volume (partial-breast irradiation) and less treatment time (hypofractionation) is consolidated in modern radiation oncology practice. Age and risk for local recurrence guide the decision-making process to electro-optimal treatment. Radiotherapy technological versatility offers multiple options for individualized (risk-age adapted) recommendations. © 2014 Federación de Sociedades Españolas de Oncología (FESEO).

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