Background: Cancer outcome is associated with circulating immune cells, including eosinophils. Here we analyze the relative eosinophil count (REC) in different breast cancer subtypes. Methods: Stage I-III breast cancer patients were included in the study and classified as REC-high vs low (cutoff 1.5%) or relative lymphocyte count (RLC)-high vs low (cutoff 17.5%). The co-primary endpoints were the breast cancer-specific survival (BCSS) or the time to treatment failure (TTF) in the REC groups. Results: Overall 930 patients were included in the study. We observed a benefit for REC-high vs REC-low in TTF (HR 0.610, 95% CI 0.458-0.812), and in BCSS (HR 0.632, 95% CI 0.433-0.923). Similarly, we observed a better TTF (HR 0.421, 95% CI 0.262-0.677) and BCSS (HR 0.350, 95% CI 0.200-0.614) in RLC-high vs low. A lower relapse rate was observed in the REC-high vs REC-low group (17.1% vs 24.7%, p = 0.005), not confirmed in the multivariate analysis. A lower median REC at baseline and at relapse was observed compared to REC after surgery and during cancer-free follow-up (p < .0001). Conclusions: REC could be a new promising, affordable and accessible predictive and prognostic biomarker in all breast cancer subtypes.

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The elimination of solid tumors largely depends on effective T-cell priming by dendritic cells (DCs). For decades, studies focusing on antitumoral immune responses have been performed with tumors transplanted subcutaneously (s.c.). These studies however do not take into account the heterogeneous tissue distribution and functionality of the different DC subsets. Given the crucial role of DCs in inducing protective immune response, we postulated that the anatomic location of tumor development may greatly impact tumor immunogenicity. We therefore implanted tumor cells either in the DC-rich dermis environment or in the s.c. tissue that mainly contains macrophages and monocytes. We showed that intradermal (i. Additional supporting information may be found in the online version of this article at the publisher's web-sited IntroductionThe concept of immunosurveillance postulates that nascent tumors are eliminated by the concerted action of innate and adaptive immune cells [1]. Cancer appearance indicates that the immune system is not always efficient at preventing tumor development, yet we have evidence that the immune system is at play in established tumors. For instance, the presence of immune cells Correspondence: Dr. Sylvie Guerder e-mail: Sylvie.guerder@inserm.fr such as natural killer (NK) and T cells within human tumors is of good prognostic value [2,3].Tumor immunogenicity is defined by its capacity to induce a protective adaptive immune response [4]. Antigenicity is an immunogenicity criterion provided that the antigen (Ag) is expressed abruptly and above a threshold concentration (antigenic discontinuum) [5]. Tumor immunogenicity also depends on environmental factors. Indeed, the tumor genetic plasticity and the local immunosuppressive tumor environment often defeat the immune system, the later mainly affecting dendritic cell (DC) recruitment and functions [4,6].C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 610 Nathalie T. Joncker et al. Eur. J. Immunol. 2016. 46: 609-618 It is now established that the DC network among lymphoid organs and peripheral tissues is highly heterogenous, at both the phenotypic and functional levels [7,8]. Given the crucial role of DCs in inducing protective immune response and their heterogenous representation in different anatomical sites, it might be expected that the anatomic location of tumor development may greatly impact tumor immunogenicity. The vast majority of studies focusing on antitumor immune responses in mouse models are performed with tumors transplanted subcutaneously (s.c.). A previous study performed in rats showed however that intradermal (i.d.) injection of tumor cells, but not s.c. injection, leads to increased tumor immunogenicity [9]. The s.c. tissue contains mainly monocytes and macrophages. In sharp contrast, the epidermis and dermis contain multiple DC subsets [10][11][12] DDCs and CD11b+ monocyte-derived inflammatory DCs (moDCs) [13][14][15][16][17][18]. The relative contribution of these different APC to tumor immunogenicity is...

The role of eosinophils, a cell type involved in the immune response to parasitic infections and allergies, has been investigated in different cancer types, in both tumor tissue and at the circulating level. Most studies showed a role mainly in conjunction with immunotherapy in melanomas and lung tumors, while few data are available in breast cancer. In this review, we summarize literature data on breast cancer, showing a prognostic role of circulating eosinophil counts as well as of the presence of tumor tissue infiltration by eosinophils. In particular, some studies showed an association between a higher circulating eosinophil count and a good prognosis, as well as an association with response to neoadjuvant chemotherapy in hormone receptor-negative/HER2-positive and in triple negative breast cancer. Several mechanistic studies have also been conducted in in vivo models, but the exact mechanism by which eosinophils act in the presence of breast cancer is still unknown. Further studies on this subject are desirable, in order to understand their role at the cellular level, identify related biomarkers and/or possibly search for new therapeutic targets.

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