Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression

Mol Oncol. 2022 Jan;16(1):88-103. doi: 10.1002/1878-0261.13047. Epub 2021 Jul 12.


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 toward 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 with non-metastatic 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 toward exhaustion and promoting immunosuppression by recruitment or increased differentiation toward Tregs. These results show that immune suppression occurs already in early stages of tumor progression.

Keywords: T-cell exhaustion; breast cancer; immune activation; immune profile; metastatic lymph nodes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / pathology
  • CD8-Positive T-Lymphocytes
  • Female
  • Humans
  • Immunosuppression Therapy
  • Lymph Nodes / pathology
  • Melanoma
  • Skin Neoplasms
  • T-Lymphocyte Subsets / pathology

Supplementary concepts

  • Melanoma, Cutaneous Malignant