Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169 macrophages by metastatic breast cancers.

BACKGROUND

Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes.

METHODS

We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients).

FINDINGS

The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169 lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36.7 ± 21.1 vs 7.3 ± 7.0 cells/mm, p = 0.0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the infiltration of CD169 macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169 macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169 macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p = 0.022).

INTERPRETATION

We concluded that lymph nodes with breast cancer metastases have fewer CD169 macrophages, which may be detrimental to the activity of anti-cancer immunity.

FUNDING

JSPS KAKENHI (16H06279, 20H03451, 20H04842, 22H04925, 19K16770, and 21K15530, 24K02236), JSPS Fellows (JP22KJ1822), AMED (JP21ck0106698), JST FOREST (JPMJFR2062), Caravel, Co., Ltd, Japan Foundation for Applied Enzymology, and Sumitomo Pharma Co., Ltd. under SKIPS.