CD169⁺ sinus macrophages in regional lymph nodes do not predict mismatch-repair status of patients with colorectal cancer

Aims: Mismatch-repair deficiency and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC) is treated with programmed death (PD)-1 antibody regardless of PD-ligand (L)1 expression in tumor cells. We previously found that abundant CD169⁺ macrophages in regional lymph node (RLN) sinuses and CD8⁺ tumor-infiltrating lymphocytes (TILs) positively correlated in CRC and were associated with a favorable prognosis. However, associations between dMMR/MSI-H CRC and CD8⁺ TILs or prognoses vary among studies. In this study, we attempted to compare the association between MMR status, CD169⁺ macrophages in RLNs, CD8⁺ TILs, PD-L1 scores, and prognoses in CRC.

Methods and results: We immunostained 83 surgically resected CRC tumors that we previously analyzed for MMR proteins, and identified 9 that were dMMR. The number of CD169⁺ macrophages in RLNs and CD8⁺ TILs significantly correlated with overall survival, whereas MMR status did not. The number of cells positive for the TIL markers CD3, CD4, CD8, and TIA-1, and macrophage markers CD68 and CD169 in RLNs did not significantly differ between groups according to MMR status. Furthermore, combined positive scores (CPS) for PD-L1 expression in five of nine dMMR CRCs were all <1. We found that dMMR in CRC did not correlate with numbers of CD169⁺ macrophages in RLNs or CD8⁺ TILs.

Conclusions: CRC with CD169⁺ macrophages in RLNs and abundant CD8⁺ TILs indicates a better prognosis and it should be immunologically classified as a different antitumor group from dMMR CRC.