Immune cells infiltrate most solid tumours, and while some of these tumour-infiltrating cells, such as CD8+ T cells, have a beneficial role in that they can destroy tumour cells, others, such as regulatory T (Treg) cells, are detrimental as they can impair anti-tumour immunity and promote tumour growth. We hypothesise that tumour-infiltrating cells leave primary tumour deposits and play a key role in regulating tumour responses in draining lymph nodes.
Using photoconvertible transgenic mice, we labelled tumour-infiltrating cells and investigated immune cell migration between primary tumours and draining lymph nodes. Although myeloid cells comprised the major tumour-infiltrating subset, flow cytometric analysis revealed that T cells were the largest tumour-egressing population. Consistent with these findings, histological sections of draining lymph nodes stained with anti-CD3 showed that the majority of tumour-egressing cells localised to the T cell zone and about 80% of these T cells were antigen-experienced. Interestingly, tumour-experienced T cells were enriched in CD4+CD25+ Treg cells as well as in γδ T cells. These subsets have previously been implicated in inducing pro- and anti-tumour immune responses respectively, thus further studies will focus on the role of these tumour-egressing subsets in shaping immune response to tumours in draining lymph nodes.
In summary, we provide the first demonstration of bidirectional cellular communication between tumours and draining lymph nodes. This communication is largely mediated by T cells and may have important implications in regulation of tumour responses.