The second important and surprising discovery was the observation that this effect was highly localized; it only occurred in the lymph nodes. These hyper-activated Tregs suppressed the natural killer cells found in the area. Those cells are an important aspect of the immune system that can detect and destroy intruders. “As long as they’re allowed to do their work, of course,” Kos says.
Interestingly, research with clinical data sets had previously connected the presence of Tregs to lymph node metastases in breast cancer, Kos knows. “But no one ever elaborated on these results. We are trying to uncover this connection further.”
Together with Tanja de Gruijl’s research group at the Amsterdam UMC, the NKI group proceeded to investigate lymph nodes that had been removed from breast cancer patients with and without metastases, as well as healthy lymph nodes from preventive mastectomies in carriers of hereditary breast cancer genes. These lymph nodes displayed the same phenomenon as the Tregs in mice.
However, the Tregs found in the lungs – another location in which metastases often occur – did not attack natural killer cells. “We currently do not know why,” Kos says. “Although we have our theories. But every organ seems to have its own mechanism. How these mechanisms behind metastases differ between the organs, and what role the immune system plays, will be a new field of research.”
This discovery is currently not very useful in the clinic, Kos states. “The system is way too complex for that. But we do know that breast cancer patients with lymph node metastases have a much lower five-year survival rate. The more you know about the processes during this early stage, the better you can learn to influence it.”
Publication: Kevin Kos et al., ‘Tumor-educated Tregs drive organ-specific metastasis in breast cancer by impairing NK cells in the lymph node niche’, Cell Reports, March 1, 2022. DOI: 10.1016/j.celrep.2022.110447.