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JOURNAL ARTICLE
Elise Ballot, Loïck Galland, Hugo Mananet, Romain Boidot, Laurent Arnould, Isabelle Desmoulins, Didier Mayeur, Courèche Kaderbhai, Silvia Ilie, Audrey Hennequin, Anthony Bergeron, Valentin Derangère, François Ghiringhelli, Caroline Truntzer, Sylvain Ladoire
PURPOSE: The vast majority of research studies that have described the links between DNA damage repair or homologous recombination deficiency (HRD) score, and tumor biology, have concerned either triple negative breast cancers or cancers with mutation of BRCA 1/2. We hypothesized that ER + /HER2- early breast tumors without BRCA 1/2 mutation could have high HRD score and aimed to describe their genomic, transcriptomic, and immune landscapes. PATIENTS AND METHODS: In this study, we reported BRCA 1/2 mutational status, HRD score, and mutational signature 3 (S3) expression, in all early breast cancer (eBC) subtypes from the TCGA database, with a particular focus in ER + /HER2-...
November 18, 2022: Breast Cancer Research: BCR
#2
REVIEW
Fanny Ledys, Laura Kalfeist, Loick Galland, Emeric Limagne, Sylvain Ladoire
Despite a few cases of long-responder patients, immunotherapy with anti-PD-(L)1 has so far proved rather disappointing in monotherapy in metastatic breast cancer, prompting the use of synergistic therapeutic combinations incorporating immunotherapy by immune-checkpoint inhibitors. In addition, a better understanding of both the mechanisms of sensitivity and resistance to immunotherapy, as well as the immunological effects of the usual treatments for breast cancer, make it possible to rationally consider this type of therapeutic combination...
November 29, 2021: Cancers
#3
JOURNAL ARTICLE
Quentin Klopfenstein, Valentin Derangère, Laurent Arnould, Marion Thibaudin, Emeric Limagne, Francois Ghiringhelli, Caroline Truntzer, Sylvain Ladoire
BACKGROUND: The prognosis of early breast cancer is linked to clinic-pathological stage and the molecular characteristics of intrinsic tumor cells. In some patients, the amount and quality of tumor-infiltrating immune cells appear to affect long term outcome. We aimed to propose a new tool to estimate immune infiltrate, and link these factors to patient prognosis according to breast cancer molecular subtypes. METHODS: We performed in silico analyses in more than 2800 early breast cancer transcriptomes with corresponding clinical annotations...
June 2021: Journal for Immunotherapy of Cancer
#4
JOURNAL ARTICLE
A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer.
Claire Bonneau, Antoine Eliès, Yann Kieffer, Brigitte Bourachot, Sylvain Ladoire, Floriane Pelon, Delphine Hequet, Jean-Marc Guinebretière, Christophe Blanchet, Anne Vincent-Salomon, Roman Rouzier, Fatima Mechta-Grigoriou
BACKGROUND: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients. METHODS: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients...
July 14, 2020: Breast Cancer Research: BCR
#5
REVIEW
Sylvain Ladoire, Valentin Derangère, Laurent Arnould, Marion Thibaudin, Bruno Coudert, Veronique Lorgis, Isabelle Desmoulins, Marie Chaix, Pierre Fumoleau, François Ghiringhelli
The role of the immune response in breast cancer is now well recognized and increasingly taken in account. The goal of this article is, in the first part, to underline its prognostic impact and to precise the immunosurvelliance, immunoselection and the immunosubversion concepts involved in the control and evasion of breast carcinoma. In the second part, therapeutic strategies for the restauration of anti-tumor immunity are developed. Vaccination strategies and checkpoints inhibitors blockade strategies are discussed as well as the immunogenic death linked to the conventional treatments of breast cancer...
February 2017: Annales de Pathologie
#6
Sylvain Ladoire, David Enot, Fabrice Andre, Laurence Zitvogel, Guido Kroemer
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...
February 2016: Oncoimmunology
#7
JOURNAL ARTICLE
Sylvain Ladoire, David Enot, Laura Senovilla, François Ghiringhelli, Vichnou Poirier-Colame, Kariman Chaba, Michaela Semeraro, Marie Chaix, Frédérique Penault-Llorca, Laurent Arnould, Marie Laure Poillot, Patrick Arveux, Suzette Delaloge, Fabrice Andre, Laurence Zitvogel, Guido Kroemer
Several cell-intrinsic alterations have poor prognostic features in human breast cancer, as exemplified by the absence of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-positive puncta in the cytoplasm (which indicates reduced autophagic flux) or the loss of nuclear HMGB1 expression by malignant cells. It is well established that breast cancer is under strong immunosurveillance, as reflected by the fact that scarce infiltration of the malignant lesion by CD8(+) cytotoxic T lymphocytes or comparatively dense infiltration by immunosuppressive cell types (such as FOXP3(+) regulatory T cells or CD68(+) tumor-associated macrophages), resulting in low CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios, has a negative prognostic impact...
May 3, 2016: Autophagy
#8
Marion Thibaudin, Marie Chaix, Romain Boidot, Frédérique Végran, Valentin Derangère, Emeric Limagne, Hélène Berger, Sylvain Ladoire, Lionel Apetoh, François Ghiringhelli
Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Rorγt and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-βand IL-6...
2016: Oncoimmunology
#9
JOURNAL ARTICLE
Erika Vacchelli, Yuting Ma, Elisa E Baracco, Antonella Sistigu, David P Enot, Federico Pietrocola, Heng Yang, Sandy Adjemian, Kariman Chaba, Michaela Semeraro, Michele Signore, Adele De Ninno, Valeria Lucarini, Francesca Peschiaroli, Luca Businaro, Annamaria Gerardino, Gwenola Manic, Thomas Ulas, Patrick Günther, Joachim L Schultze, Oliver Kepp, Gautier Stoll, Céline Lefebvre, Claire Mulot, Francesca Castoldi, Sylvie Rusakiewicz, Sylvain Ladoire, Lionel Apetoh, José Manuel Bravo-San Pedro, Monica Lucattelli, Cécile Delarasse, Valérie Boige, Michel Ducreux, Suzette Delaloge, Christophe Borg, Fabrice André, Giovanna Schiavoni, Ilio Vitale, Pierre Laurent-Puig, Fabrizio Mattei, Laurence Zitvogel, Guido Kroemer
Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer. We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1(-/-) mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity...
November 20, 2015: Science
#10
RANDOMIZED CONTROLLED TRIAL
Antonella Sistigu, Takahiro Yamazaki, Erika Vacchelli, Kariman Chaba, David P Enot, Julien Adam, Ilio Vitale, Aicha Goubar, Elisa E Baracco, Catarina Remédios, Laetitia Fend, Dalil Hannani, Laetitia Aymeric, Yuting Ma, Mireia Niso-Santano, Oliver Kepp, Joachim L Schultze, Thomas Tüting, Filippo Belardelli, Laura Bracci, Valentina La Sorsa, Giovanna Ziccheddu, Paola Sestili, Francesca Urbani, Mauro Delorenzi, Magali Lacroix-Triki, Virginie Quidville, Rosa Conforti, Jean-Philippe Spano, Lajos Pusztai, Vichnou Poirier-Colame, Suzette Delaloge, Frederique Penault-Llorca, Sylvain Ladoire, Laurent Arnould, Joanna Cyrta, Marie-Charlotte Dessoliers, Alexander Eggermont, Marco E Bianchi, Mikael Pittet, Camilla Engblom, Christina Pfirschke, Xavier Préville, Gilles Uzè, Robert D Schreiber, Melvyn T Chow, Mark J Smyth, Enrico Proietti, Fabrice André, Guido Kroemer, Laurence Zitvogel
Some of the anti-neoplastic effects of anthracyclines in mice originate from the induction of innate and T cell-mediated anticancer immune responses. Here we demonstrate that anthracyclines stimulate the rapid production of type I interferons (IFNs) by malignant cells after activation of the endosomal pattern recognition receptor Toll-like receptor 3 (TLR3). By binding to IFN-α and IFN-β receptors (IFNARs) on neoplastic cells, type I IFNs trigger autocrine and paracrine circuitries that result in the release of chemokine (C-X-C motif) ligand 10 (CXCL10)...
November 2014: Nature Medicine
#11
JOURNAL ARTICLE
S Ladoire, L Arnould, G Mignot, L Apetoh, C Rébé, F Martin, P Fumoleau, B Coudert, F Ghiringhelli
BACKGROUND: In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival...
July 26, 2011: British Journal of Cancer
#12
MULTICENTER STUDY
Sylvain Ladoire, Grégoire Mignot, Sandrine Dabakuyo, Laurent Arnould, Lionel Apetoh, Cedric Rébé, Bruno Coudert, Francois Martin, Marie Hélène Bizollon, André Vanoli, Charles Coutant, Pierre Fumoleau, Franck Bonnetain, François Ghiringhelli
Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy...
July 2011: Journal of Pathology
#13
JOURNAL ARTICLE
Sylvain Ladoire, Laurent Arnould, Lionel Apetoh, Bruno Coudert, Francois Martin, Bruno Chauffert, Pierre Fumoleau, François Ghiringhelli
PURPOSE: T-cell infiltration is associated with good tumor prognosis in many cancers. To assess the capacity of neoadjuvant chemotherapy to affect T-cell infiltration in breast cancer, we evaluated CD3 and CD8 infiltrates, and the Foxp3 immunosuppressive T cells. EXPERIMENTAL DESIGN: CD3+, CD8+, and Foxp3+ cell infiltrates were detected by immunohistochemistry in a series of 56 breast cancer patients before and after the end of neoadjuvant chemotherapy. RESULTS: Poor prognostic factors (negative hormonal receptors, high tumor grade, and nodal involvement) were associated with a significantly higher number of CD3, CD8, and Foxp3 infiltrates before the beginning of chemotherapy...
April 15, 2008: Clinical Cancer Research
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