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.
Author Info: (1) Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. (2) Department of Cancer Im
Author Info: (1) Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. (2) Department of Cancer Immunology, Institute for Cancer Research, Division of Cancer Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway. KG Jebsen centre for B-cell malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. (3) Department of Cancer Immunology, Institute for Cancer Research, Division of Cancer Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway. KG Jebsen centre for B-cell malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. (4) Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Radiumhospitalet Oslo, Norway. (5) Institute for Cancer Genetics and Informatics, Division of Cancer Medicine, Oslo University Hospital, Radiumhospitalet Oslo, Norway. Department of Informatics, University of Oslo, Oslo, Norway. Nuffield Division of Clinical Laboratory Sciences, University of Oxford, United Kingdom. (6) Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway. (7) Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway. (8) Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway. (9) Oslo Breast Cancer Consortium, Oslo University Hospital, Oslo, Norway. (10) Institute for Bioinformatics, University of Oslo, Oslo, Norway. (11) Department of Cancer Immunology, Institute for Cancer Research, Division of Cancer Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway. KG Jebsen centre for B-cell malignancies, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. (12) Department of Cancer Genetics, Institute for Cancer Research, Division of Cancer Medicine, Oslo University Hospital, Radiumhospitalet, Oslo, Norway. Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway.
