F. Bray, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA. Cancer J. Clin, 2018.

G. Tagliabue, Atmospheric fine particulate matter and breast cancer mortality: A populationbased cohort study, BMJ Open, 2016.

E. S. Schernhammer, Rotating night shifts and risk of breast cancer in women participating in the nurses' health study, J. Natl. Cancer Inst, 2001.

J. Hansen, Night Shift Work and Risk of Breast Cancer, Current environmental health reports, 2017.

L. B. Samuelsson, D. H. Bovbjerg, K. A. Roecklein, and M. H. Hall, Sleep and circadian disruption and incident breast cancer risk: An evidence-based and theoretical review, Neuroscience and Biobehavioral Reviews, 2018.

E. Cordina-duverger, Night shift work and breast cancer: a pooled analysis of populationbased case-control studies with complete work history, Eur. J. Epidemiol, 2018.

S. Mocellin, S. Tropea, C. Benna, and C. R. Rossi, Circadian pathway genetic variation and cancer risk: Evidence from genome-wide association studies, BMC Med, 2018.

C. Cadenas, Loss of circadian clock gene expression is associated with tumor progression in breast cancer, Cell Cycle, vol.13, pp.3282-3291, 2014.

C. M. Mcqueen, PER2 regulation of mammary gland development, Dev, 2018.

M. J. Boden, T. J. Varcoe, A. Voultsios, and D. J. Kennaway, Reproductive biology of female Bmal1 null mice, Reproduction, 2010.

K. Hoshino, Y. Wakatsuki, M. Iigo, and S. Shibata, Circadian Clock mutation in dams disrupts nursing behavior and growth of pups, Endocrinology, 2006.

N. Yang, Cellular mechano-environment regulates the mammary circadian clock, Nat. Commun, 2017.

W. W. Hwang-verslues, Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy, Proc. Natl. Acad. Sci. U. S. A, vol.110, pp.12331-12337, 2013.

K. C. Van-dycke, Chronically Alternating Light Cycles Increase Breast Cancer Risk in Mice, Curr. Biol, 2015.

C. T. Guy, R. D. Cardiff, and W. J. Muller, Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease, Mol. Cell. Biol, vol.12, pp.954-961, 1992.

E. Filipski, Effects of chronic jet lag on tumor progression in mice, Cancer Res, 2004.

H. Oike, M. Sakurai, K. Ippoushi, and M. Kobori, Time-fixed feeding prevents obesity induced by chronic advances of light/dark cycles in mouse models of jet-lag/shift work, Biochem. Biophys. Res. Commun, 2015.

L. P. Casiraghi, A. Alzamendi, A. Giovambattista, J. J. Chiesa, and D. A. Golombek, Effects of chronic forced circadian desynchronization on body weight and metabolism in male mice, Physiol. Rep, 2016.

M. Shackleton, Generation of a functional mammary gland from a single stem cell, Nature, 2006.

E. Y. Lin, Progression to Malignancy in the Polyoma Middle T Oncoprotein Mouse Breast Cancer Model Provides a Reliable Model for Human Diseases, Am. J. Pathol, issue.10, pp.63568-63575, 2003.

S. A. Mani, The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells, Cell, vol.133, pp.704-715, 2008.

P. Morel, Generation of breast cancer stem cells through epithelial-mesenchymal transition, PLoS One, vol.3, p.2888, 2008.

H. Acloque, M. S. Adams, K. Fishwick, M. Bronner-fraser, and M. A. Nieto, Epithelialmesenchymal transitions: The importance of changing cell state in development and disease, J. Clin. Invest, vol.119, 2009.
URL : https://hal.archives-ouvertes.fr/hal-02912722

J. Stingl, Purification and unique properties of mammary epithelial stem cells, Nature, 2006.

J. E. Visvader and J. Stingl, Mammary stem cells and the differentiation hierarchy: Current status and perspectives, Genes and Development, 2014.

A. Vassilopoulos, C. Chisholm, T. Lahusen, H. Zheng, and C. X. Deng, A critical role of CD29 and CD49f in mediating metastasis for cancer-initiating cells isolated from a Brca1-associated mouse model of breast cancer, Oncogene, 2014.

L. Fu, H. Pelicano, J. Liu, P. Huang, and C. C. Lee, The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo, Cell, pp.961-964, 2002.

E. Hadadi, L. E. Souza, . De, A. Bennaceur-griscelli, and H. Acloque, Identification of valid reference genes for circadian gene-expression studies in human mammary epithelial cells, Chronobiol. Int, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02621939

K. Movahedi, Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes, Cancer Res, 2010.

R. A. Franklin, The cellular and molecular origin of tumor-associated macrophages, Science, p.80, 2014.

K. Wang, T. Shen, G. P. Siegal, and S. Wei, The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer, Hum. Pathol, 2017.

A. Müller, Involvement of chemokine receptors in breast cancer metastasis, Nature, 2001.

G. Helbig, NF-?B promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4, J. Biol. Chem, 2003.

C. W. Steele, CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma, Cancer Cell, 2016.

M. Sano, Blocking CXCLs-CXCR2 axis in tumor-stromal interactions contributes to survival in a mouse model of pancreatic ductal adenocarcinoma through reduced cell invasion/migration and a shift of immune-inflammatory microenvironment, Oncogenesis, 2019.

M. Bradley, M. Bond, J. Manini, Z. Brown, and S. Charlton, SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor, Br. J. Pharmacol, 2009.

S. Acharyya, A CXCL1 paracrine network links cancer chemoresistance and metastasis, Cell, 2012.

S. E. Sephton, Diurnal cortisol rhythm as a predictor of lung cancer survival, Brain. Behav. Immun, 2013.

D. Vlachou, G. A. Bjarnason, S. Giacchetti, F. Lévi, and D. A. Rand, TimeTeller: a New Tool for Precision Circadian Medicine and Cancer Prognosis, bioRxiv, 2019.

X. Ye, Distinct EMT programs control normal mammary stem cells and tumour-initiating cells, Nature, vol.525, pp.256-260, 2015.

K. R. Fischer, Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance, Nature, 2015.

D. P. Hollern, M. R. Swiatnicki, and E. R. Andrechek, Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers, PLoS Genet, 2018.

F. Delaunay and V. Laudet, Circadian clock and microarrays: Mammalian genome gets rhythm, Trends in Genetics, 2002.
URL : https://hal.archives-ouvertes.fr/hal-00077640

X. Pan, X. C. Jiang, and M. M. Hussain, Impaired cholesterol metabolism and enhanced atherosclerosis in clock Mutant Mice, Circulation, 2013.

D. Gnocchi, M. Pedrelli, E. Hurt-camejo, and P. Parini, Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism, 2015.

C. S. Mcalpine and F. K. Swirski, Circadian influence on metabolism and inflammation in atherosclerosis, Circulation Research, 2016.

S. Q. Shi, T. S. Ansari, O. P. Mcguinness, D. H. Wasserman, and C. H. Johnson, Circadian disruption leads to insulin resistance and obesity, Curr. Biol, 2013.

N. M. Kettner, Circadian dysfunction induces leptin resistance in mice, Cell Metab, 2015.

J. Qian, B. Yeh, K. Rakshit, C. S. Colwell, and A. V. Matveyenko, Circadian disruption and dietinduced obesity synergize to promote development of ? -cell failure and diabetes in male rats, Endocrinology, 2015.

R. D. Rudic, BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis, PLoS Biol, 2004.

H. Hojo, Remote reprogramming of hepatic circadian transcriptome by breast cancer, Oncotarget, 2017.

S. Masri, Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis, Cell, vol.165, pp.896-909, 2016.

E. Filipski, Effects of light and food schedules on liver and tumor molecular clocks in mice, J. Natl. Cancer Inst, 2005.

X. M. Li, Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing, Cancer Res, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00497206

T. Papagiannakopoulos, Circadian Rhythm Disruption Promotes Lung Tumorigenesis, Cell Metab, 2016.

J. Climent, Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer, J. Clin. Oncol, 2010.

T. Oshima, Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer, Oncol. Rep, 2011.

H. Cheng, Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors, Hum. Mol. Genet, 2004.

N. J. Mollema, Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina, PLoS One, 2011.

A. Ahumada, Signaling of rat frizzled-2 through phosphodiesterase and cyclic GMP. Science (80-. ), 2002.

H. Wang, Y. Lee, and C. C. Malbon, PDE6 is an effector for the Wnt/Ca 2+ /cGMP-signalling pathway in development, Biochem. Soc. Trans, 2004.

P. S. Welz, BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis, Cell, 2019.

K. B. Koronowski, Defining the Independence of the Liver Circadian Clock, Cell, 2019.

L. Mao, Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3?, Mol. Endocrinol, vol.26, pp.1808-1828, 2012.

A. W. Lambert, D. R. Pattabiraman, and R. A. Weinberg, Emerging Biological Principles of Metastasis, Cell, 2017.

C. Vandewalle, SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions, Nucleic Acids Res, 2005.

S. A. Mani, Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers, Proc. Natl. Acad. Sci, 2007.

M. Bashir, S. Damineni, G. Mukherjee, and P. Kondaiah, Activin-a signaling promotes epithelialmesenchymal transition, invasion, and metastatic growth of breast cancer, npj Breast Cancer, 2015.

O. Ocaña, Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1, Cancer Cell, vol.22, 2012.

A. Grosse-wilde, Stemness of the hybrid epithelial/mesenchymal state in breast cancer and its association with poor survival, Chronobiol. Int, 2013.

S. J. Carter, A matter of time: study of circadian clocks and their role in inflammation, J. Leukoc. Biol, 2016.

C. Scheiermann, J. Gibbs, L. Ince, and A. Loudon, Clocking in to immunity, Nature Reviews Immunology, 2018.

S. Sukumaran, W. J. Jusko, D. C. Dubois, and R. R. Almon, Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action, J. Appl. Physiol, 2011.

O. Pluquet, Posttranscriptional regulation of per1 underlies the oncogenic function of IRE?, Cancer Res, 2013.
URL : https://hal.archives-ouvertes.fr/hal-02400356

J. Gibbs, An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action, Nat. Med, 2014.

W. He, Circadian Expression of Migratory Factors Establishes Lineage-Specific Signatures that Guide the Homing of Leukocyte Subsets to Tissues, Immunity, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02143556

D. I. Gabrilovich and S. Nagaraj, Myeloid-derived suppressor cells as regulators of the immune system, Nature Reviews Immunology, 2009.

D. Lindau, P. Gielen, M. Kroesen, P. Wesseling, and G. J. Adema, The immunosuppressive tumour network: Myeloid-derived suppressor cells, regulatory T cells and natural killer T cells, Immunology, 2013.

J. Michaeli, Tumor-associated neutrophils induce apoptosis of non-activated CD8 T-cells in a TNF? and NO-dependent mechanism, promoting a tumor-supportive environment, Oncoimmunology, 2017.

S. Feng, Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers, Proc. Natl. Acad. Sci, 2018.

E. Peranzoni, Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment, Proc. Natl. Acad. Sci, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01791995

Y. Cheng, X. Ma, Y. Wei, and X. W. Wei, Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases, Biochimica et Biophysica Acta -Reviews on Cancer, 2019.

J. Hol, L. Wilhelmsen, and G. Haraldsen, The murine IL-8 homologues KC, MIP-2, and LIX are found in endothelial cytoplasmic granules but not in Weibel-Palade bodies, J. Leukoc. Biol, 2010.

S. Méndez-ferrer, D. Lucas, M. Battista, and P. S. Frenette, Haematopoietic stem cell release is regulated by circadian oscillations, Nature, 2008.

Y. Zhao, Uncovering the mystery of opposite circadian rhythms between mouse and human leukocytes in humanized mice, Blood, 2017.

N. Nagarsheth, M. S. Wicha, and W. Zou, Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy, Nature Reviews Immunology, 2017.

I. X. Chen, Blocking CXCR4 alleviates desmoplasia, increases T-lymphocyte infiltration, and improves immunotherapy in metastatic breast cancer, Proc. Natl. Acad. Sci, 2019.

L. V. De-assis, Expression of the Circadian Clock Gene BMAL1 Positively Correlates With Antitumor Immunity and Patient Survival in Metastatic Melanoma, Front. Oncol, 2018.

T. M. Paine, H. D. Soule, R. J. Pauley, and P. J. Dawson, Characterization of epithelial phenotypes in mortal and immortal human breast cells, Int. J. Cancer, 1992.

B. Li, C. N. Dewey, and . Rsem, Accurate transcript quantification from RNA-seq data with or without a reference genome, Bioinformatics: The Impact of Accurate Quantification on Proteomic and Genetic Analysis and Research, 2014.

Z. Gu, R. Eils, and M. Schlesner, Complex heatmaps reveal patterns and correlations in multidimensional genomic data, Bioinformatics, 2016.

F. Rohart, B. Gautier, A. Singh, and K. A. Lê-cao, mixOmics: An R package for 'omics feature selection and multiple data integration, PLoS Comput. Biol, 2017.

M. I. Love, W. Huber, S. Anders, and . Deseq2, Genome Biol, 2014.

A. Federico, S. Monti, and . Hyper, An R Package for Geneset Enrichment Workflows. bioRxiv, 2019.

, Number of positive tumour infiltrated immune cells for CXCR2 in LD (n=11) and JL (n=8) samples. Data are shown as scatter dot plot with lines representing median with interquartile

, The percentage of disseminated tumour cells in BM and peripheral blood in vehicle (n=4) and SB265610 (n=6) group. Data are presented as scatter dot plot with lines representing median with interquartile. p-values are calculated from an unpaired t-test. (G) Percentage of tumour infiltrating immune cells (TIC) in vehicle (n=5) and SB265610 (n=6) cohort. Data are presented as scatter dot plot with lines representing median with interquartile. p-values are calculated from an unpaired t-test. (H) Relative distribution of lymphoid and myeloid compartment of TIC in both cohorts, Effects of Cxcr2 axis inhibition on tumour development in JL mice: (D) Scheme illustrating the treatment flow

, It increases the proportion of cancer stem cells (CSCs, in dark blue)) and modifies the tumour microenvironment (TME) through the recruitment of myeloid-derived suppressor cells (MDSCs, in yellow) leading to a suppressive tumour immune microenvironment (TIME)