Single-cell analysis reveals tumour size as a key driver of immune cell profile alterations in primary breast tumours and corresponding lymph nodes.

BACKGROUND: At diagnosis, 30-40% of women with breast cancer have metastases in sentinel (SN) or axillary lymph nodes (ALN). Nodal status is a strong prognostic factor and guides treatment decisions. Immune checkpoint inhibition has shown some efficacy, which can increase in the neoadjuvant setting. A better understanding of how tumour cells in primary tumours and metastatic lymph nodes shape the local immune microenvironment may provide clues for more individualized therapeutic interventions. METHODS: We conducted deep immunophenotypic analysis of 29 primary breast tumours and 36 lymph nodes from 38 patients with primary operable breast cancer. RESULTS: The immune profile of the primary tumour was not predictive of the lymph node immune profile or metastatic status. Primary tumours showed prominent CD8 T cell exhaustion and activated regulatory T cells, and the frequencies of these subsets were associated with tumour size. The immune cell profile in lymph nodes were different from the profile in primary tumours, except for the ALN+ nodes, which displayed a T-cell profile more similar to primary tumours. The frequencies of the T cell subsets in lymph nodeswere associated with metastatic size. Tumour cells from smaller metastases exhibited a distinct phenotype compared to those from larger tumour deposits, and the size of the tumour cell deposit impacted the local immune cell composition. CONCLUSION: The tumour size of primary tumours and metastatic size in lymph nodes are the main drivers of changes in immune cell composition.