Rye and Huse et al. used mass cytometry to probe lymph nodes (LNs) from 52 breast cancer patients at different stages of metastasis. Compared to non-metastatic sentinel LNs, metastatic axillary LNs had increased CD8+ T cell frequency (reduced CD4/CD8 ratio), TIGIT, and PD-1 expression among T cells, and an activated Treg proportion. TIGIT ligands CD155/CD112 were expressed on tumor cells, and TIGIT+ T cells had reduced ERK phosphorylation, indicating a functional reduction in TCR signaling. Through IHC, the shift from CD4+ to CD8+ T cells was found to be most pronounced within tumor areas of the LN, and Tregs colocalized with CD8+ T cells.
Contributed by Alex Najibi
ABSTRACT: Sentinel lymph nodes are the first nodes draining the lymph from a breast, and could reveal early changes in the host immune system upon dissemination of breast cancer cells. To investigate this, we performed single-cell immune profiling of lymph nodes with and without metastatic cells. Whereas no significant changes were observed for B-cell and natural killer (NK)-cell subsets, metastatic lymph nodes had a significantly increased frequency of CD8 T cells and a skewing towards an effector/memory phenotype of CD4 and CD8 T cells, suggesting an ongoing immune response. Additionally, metastatic lymph nodes had an increased frequency of TIGIT (T cell immunoreceptor with Ig and ITIM domains)-positive T cells with suppressed TCR signaling compared to non-metastatice nodes, indicating exhaustion of effector T cells, and an increased frequency of regulatory T cells (Tregs) with an activated phenotype. T-cell alterations correlated with the percentage of metastatic tumor cells, reflecting the presence of metastatic tumor cells driving T effector cells towards exhaustion and promoting immunosuppression by recruitment or increased differentiation towards Tregs.These results show that immune supression occure already in early stages of tumor progression.