Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells

Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1?? and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1??, IL-6 and IFN-??. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth.ope

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion

Influence of Tumor Location on the Composition of Immune Infiltrate and Its Impact on Patient Survival. Lessons from DCBCL and Animal Models

International audienceDiffuse large B-cell lymphomas (DLBCLs) are heterogeneous diseases growing either in nodal or extranodal locations including the central nervous system. One key issue is to decipher the prognostic value of immune cells infiltrating these tumors as DLBCLs developing in sanctuaries are more aggressive than nodal DLCBLs. Here, we summarize available data from the literature regarding the prognostic values of the different immune cell types found in these two types of human primary tumors (i.e., nodal vs brain). In nodal DLBCLs, memory T-cells and dendritic cells (DCs) densities are of good prognostic value whereas the influence of regulatory T-cells (Tregs) is less clear, in accordance with other types of cancers. Data for primary central nervous system lymphomas are very sparse for these cell types. By contrast, CD8(+) cytotoxic T-cells seem to be of poor prognosis in either location. Their presence is linked to a loss of MHC expression providing a possible immune escape mechanism for these tumors. Clearly, tumor-associated macrophages are not associated to a significant prognostic value even in the brain where they highly infiltrate the tumor. Animal models indicate some specific features of lymphoma developing in sanctuaries by comparison to splenic location, with a higher infiltration of Tregs and less DCs, most likely reflecting the immunosuppressive context of these organs. All these informations illustrate the high impact of the immune system on patient outcome, encourage the pursuit of the immune environment's analysis and of immunotherapeutic approaches

Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines

Pricop L, Redecha P, Teillaud JL, et al. Differential modulation of stimulatory and inhibitory Fc gamma receptors on human monocytes by Th1 and Th2 cytokines. JOURNAL OF IMMUNOLOGY. 2001;166(1):531-537.Immune complex-mediated inflammatory responses are initiated by Fc gammaR on phagocytes, We report in this study that an inhibitory receptor, Fc gamma RIIb2, is expressed on circulating human monocytes, and when co-cross-linked with stimulatory Fc gammaR it down-regulates effector function. Fc gamma RIIb2 expression is increased by IL-4 and decreased by IFN-gamma, in contrast to the activating receptor, Fc gamma RIIa, which is increased by IFN-gamma and decreased by IL-4, Thus, Th1 and Th2 cytokines differentially regulate the opposing Fc gammaR systems, altering the balance of activating and inhibiting Fc gammaR, The detection and cytokine modulation of Fc gamma RIIb2 in human myeloid cells provide evidence of a negative regulator of immune complex-mediated responses in human phagocytes and offer a new approach to limit Ab-triggered inflammation in autoimmune disease