AbstractAimsMismatch‐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 ResultsWe 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.ConclusionsCRC 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.