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Stoll G.,University of Paris Descartes | Stoll G.,French Institute of Health and Medical Research | Enot D.,Metabolomics and Cell Biology Platforms | Mlecnik B.,University of Paris Descartes | And 11 more authors.
OncoImmunology | Year: 2014

There is ample evidence that neoadjuvant chemotherapy of breast carcinoma is particularly efficient if the tumor presents signs of either a pre-existent or therapy-induced anticancer immune response. Antineoplastic chemotherapies are particularly beneficial if they succeed in inducing immunogenic cell death, hence converting the tumor into its own therapeutic vaccine. Immunogenic cell death is characterized by a pre-mortem stress response including endoplasmic reticulum stress and autophagy. Based on these premises, we attempted to identify metagenes that reflect an intratumoral immune response or local stress responses in the transcriptomes of breast cancer patients. No consistent correlations between immune- and stress-related metagenes could be identified across several cohorts of patients, representing a total of 1045 mammary carcinomas. Moreover, few if any, of the stress-relevant metagenes influenced the probability of pathological complete response to chemotherapy. In contrast, several immune-relevant metagenes had a significant positive impact on response rates. This applies in particular to a CXCL 13-centered, highly reproducible metagene signature reflecting the intratumoral presence of interferon-γ-producing T cells. © 2014 Landes Bioscience. Source


Ladoire S.,Georges Francois Leclerc Center | Ladoire S.,French Institute of Health and Medical Research | Enot D.,Metabolomics and Cell Biology Platforms | Senovilla L.,University Pierre and Marie Curie | And 9 more authors.
OncoImmunology | Year: 2016

In human breast cancer cells, the presence of cytoplasmic dots positive for microtubule-associated proteins 1A/1B light chain 3B (LC3B) indicates enhanced autophagic flux and favorable prognosis. LC3B+ puncta within malignant cells positively correlate with the intratumoral abundance of CD8+ cytotoxic T lymphocytes, yet negatively correlate with the frequency of local FOXP3+ regulatory T cells and CD68+ tumor-associated macrophages, resulting in an improvement of CD8+/FOXP+ or CD8+/CD68+ ratios. © 2016 Taylor & Francis Group, LLC. Source


Ladoire S.,Georges Francois Leclerc Center | Ladoire S.,French Institute of Health and Medical Research | Penault-Llorca F.,Center Jean Perrin | Penault-Llorca F.,University of Auvergne | And 19 more authors.
Autophagy | Year: 2015

In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B+ puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B+ puncta reflects increased autophagic flux. After setting optimal thresholds in the test cohort, cytoplasmic LC3B+ puncta and nuclear HMGB1 were scored as positive in 27.2% and 28.6% of the tumors, respectively, in the validation cohort, while 8.7% were considered as double positive. LC3B+ puncta or HMGB1 expression alone did not constitute independent prognostic factors for metastasis-free survival (MFS) in multivariate analyses. However, the combined positivity for LC3B+ puncta and nuclear HMGB1 constituted an independent prognostic factor significantly associated with prolonged MFS (hazard ratio: 0.49 95% confidence interval [0.26–0.89]; P D 0.02), and improved breast cancer specific survival (hazard ratio: 0.21 95% confidence interval [0.05–0.85]; P D 0.029). Subgroup analyses revealed that within patients with poor-prognosis BC, HMGB1+ LC3B+ double-positive tumors had a better prognosis than BC that lacked one or both of these markers. Altogether, these results suggest that the combined positivity for LC3B+ puncta and nuclear HMGB1 is a positive predictor for longer BC survival. © 2015 Taylor and Francis Group, LLC. Source


Ladoire S.,Georges Francois Leclerc Center | Ladoire S.,University of Burgundy | Ladoire S.,French Institute of Health and Medical Research | Enot D.,Metabolomics and Cell Biology Platforms | And 7 more authors.
OncoImmunology | Year: 2016

It is well established that the anticancer immune response determines the success of anthracycline-based adjuvant chemotherapy of breast cancer. This effect is in part due to the capacity of anthracyclines to induce immunogenic cell death (ICD), a cell death modality that is preceded by autophagy and followed by HMGB1 release. Recent data on 1,798 mammary carcinoma specimens indicate that patients harboring neoplastic cells that lack immunohistochemical signs of autophagy or that have lost HMGB1 expression have indeed a poor prognosis. © 2016 Taylor & Francis Group, LLC. Source


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. Source

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