Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Laboratory of Biomaterials, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Cancer Med. 2023 May;12(9):10199-10211. doi: 10.1002/cam4.5747. Epub 2023 Feb 27.
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.
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.
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.
错配修复缺陷和微卫星高度不稳定（dMMR/MSI-H）结直肠癌（CRC）无论肿瘤细胞中 PD-配体（L）1 的表达如何，均采用程序性死亡（PD）-1 抗体进行治疗。我们之前发现，在 CRC 中，区域淋巴结（RLN）窦内丰富的 CD169 巨噬细胞与 CD8 肿瘤浸润淋巴细胞（TIL）呈正相关，并且与良好的预后相关。然而，dMMR/MSI-H CRC 与 CD8 TIL 或预后之间的关联在不同的研究中有所不同。在这项研究中，我们试图比较 MMR 状态、RLN 中的 CD169 巨噬细胞、CD8 TIL、PD-L1 评分与 CRC 预后之间的关系。
我们对 83 例先前分析过 MMR 蛋白的手术切除 CRC 肿瘤进行了免疫染色，鉴定出 9 例为 dMMR。RLN 中的 CD169 巨噬细胞数量和 CD8 TIL 数量与总生存期显著相关，而 MMR 状态则没有。根据 MMR 状态，RLN 中 TIL 标志物 CD3、CD4、CD8 和 TIA-1 以及巨噬细胞标志物 CD68 和 CD169 阳性细胞的数量在各组之间没有显著差异。此外，在 9 例 dMMR CRC 中，5 例的 PD-L1 表达的联合阳性评分（CPS）均<1。我们发现，CRC 中的 dMMR 与 RLN 中 CD169 巨噬细胞或 CD8 TIL 的数量无关。
RLN 中 CD169 巨噬细胞和丰富的 CD8 TIL 的 CRC 预示着更好的预后，它应该被免疫分类为与 dMMR CRC 不同的抗肿瘤群体。
