Mature dendritic cells (DCs) have been shown to infiltrate breast tumours, clustering with CD4+ T cells, but their influence on tumour progression was not known. Now, Palucka and colleagues show that mature DCs are instructed by breast cancer cells to induce CD4+ T cells that promote early tumour development and that neutralization of interleukin-13 (IL-13) partially prevents this acceleration in tumour development.

In this study, the authors used sublethally irradiated immunodeficient NOD-scid B2m−/− (non-obese diabetic; severe combined immunodeficiency; β2-microglobulin) mice, which lack mature T and B cells and do not express MHC class I molecules. These mice received human CD34+ haematopoietic progenitor cells (HPCs), which allows for the development of human DCs and B cells in these mice, and were implanted with human Hs578T breast cancer cells followed by the adoptive transfer of human T cells. Using this humanized mouse model, the authors could examine the role of T cells and DCs in human breast cancer progression.

Adoptive transfer of CD4+ T cells to the humanized mice 1 week after injection of Hs578T cells greatly accelerated the development of breast cancers compared with mice that did not receive T cells, indicating a role for CD4+ T cells in promoting tumour growth. Interestingly, the transfer of CD4+ T cells to immunodeficient NOD-scid B2m−/− mice that were injected with Hs578T cells but that had not received HPCs (and therefore lack human DCs and B cells) did not affect tumour size. However, co-administration of autologous DCs with CD4+ T cells promoted the development of tumours in these mice, indicating that CD4+ T cells require DCs to promote breast cancer tumour growth.

DCs isolated from the draining lymph nodes or tumours of humanized mice in which breast cancer tumours had established without adoptively transferred CD4+ T cells induced the secretion of IL-2, interferon-γ, IL-4 and IL-13 from allogeneic CD4+ T cells in vitro. Importantly, this ability of DCs to induce IL-4 and IL-13 production by CD4+ T cells was specific to breast cancer, as DCs isolated from the draining lymph nodes of melanoma tumours induced significantly less IL-4 and IL-13 production. This indicates that the breast cancer cells might directly instruct DCs to induce IL-4 and IL-13 production by CD4+ T cells.

Neutralization of IL-13 in humanized mice with Hs578T tumours and transferred CD4+ T cells partially prevented accelerated tumour development, indicating an important role for IL-13 in early tumour growth. Interestingly, the authors showed that human breast cancer cells express IL-13 and phosphorylated signal transducer and activator of transcription 6 (STAT6), which indicates that IL-13 might deliver a signal directly to cancer cells.

So, this study suggests a mechanism whereby breast cancer cells modulate the immune system through DCs to induce CD4+ T cells that promote early tumour growth. It also indicates a potential role for IL-13 in the pathophysiology of breast cancer.