Human tumors are infiltrated by dendritic cells. Yet tumor growth indicates the lack of effective anti-tumor immunity. To understand how tumors modulate DC function, we have developed a novel model to study the in vivo interactions between human cancer and human dendritic cells in an immunodeficient mouse. NOD-SCID beta2m-/- mice engrafted with human CD34+ hematopoietic progenitors develop myeloid and plasmacytoid DCs. Human tumor cell lines, such as breast cancer and melanoma, can develop in these animals (OncoHumouse). We demonstrate that these tumors differentially attract human DC and monocytes / macrophages in vivo. Indeed, breast cancer attracts larger numbers of human DCs and promotes their maturation and migration to the draining lymph nodes. This differential modulation of human DCs could be explained by different chemokine environnement observed in vivo as breast tumor secreted mostly MCP1 and IL6 and melanoma produced IL8. DC were functional as assessed by their capacity to induce allogeneic CD4 proliferation ex vivo and their ability to prime T cells against the tumor in vivo. Furthermore, DC isolated from breast tumor and its draining lymph nodes, as opposed to DC from spleen or BM, induced the production of high level of IL4, IL13 and TNF by naive CD4 T cells, suggesting that breast tumor modulate DC to induce an inflammatory Th2 response. Thus, OncoHumouse can be used to study the development and modulation of tumor immunity.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]