The present study analyzed the expression of five independent immunohistochemical markers, CD4, CD8, CD66b, CD68, and CD163, on immune cells within the colorectal cancer (CRC) tumor microenvironment (TME). Using hierarchical clustering, patients were successfully classified according to significant associations with clinicopathological features and/or survival. Patients with mismatch repair-proficient (pMMR) CRC were categorized into four groups with survival differences (p = 0.0084): CD4^Low, CD4^High, MΦ^High, and CD8^Low. MΦ^High tumors showed significantly higher expression of CD47 (p < 0.0001), a phagocytosis checkpoint molecule. These tumors contained significantly greater numbers of PD-1+ (p < 0.0001), TIM-3+ (p < 0.0001), and SIRPA+ (p < 0.0001) immune cells. Notably, 10% of the patients with pMMR CRC expressed PD-L1 (CD274) on tumor cells with significantly worse survival (p = 0.00064). The Cox proportional hazards model identified MΦ ^High (hazard ratio [HR] = 2.02, 95%, p = 0.032), CD8^Low (HR = 2.45, p = 0.011), and tumor PD-L1 expression (HR = 2.74, p = 0.0061) as potential risk factors. PD-L1–PD-1 and/or CD47–SIRPA axes targeting immune checkpoint therapies might be considered for patients with pMMR CRC according to their tumor cells and tumor immune microenvironment characteristics.

中文翻译：

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通过五种免疫细胞标记物的层次聚类分析表征结直肠癌

本研究分析了结直肠癌 (CRC) 肿瘤微环境 (TME) 内免疫细胞上五种独立的免疫组织化学标记物 CD4、CD8、CD66b、CD68 和 CD163 的表达。使用层次聚类，根据与临床病理特征和/或生存的显着关联成功对患者进行分类。错配修复良好 (pMMR) CRC 患者被分为四组，生存率存在差异 ( p  = 0.0084)：CD4^低、CD4^高、MΦ^高和 CD8^低。MΦ^高肿瘤显示 CD47（ 一种吞噬检查点分子）的表达显着升高（p < 0.0001）。这些肿瘤含有明显更多数量的 PD-1+ ( p  < 0.0001)、TIM-3+ ( p  < 0.0001) 和 SIRPA+ ( p  < 0.0001) 免疫细胞。值得注意的是，10% 的 pMMR CRC 患者在肿瘤细胞上表达 PD-L1 (CD274)，且存活率明显较差 ( p  = 0.00064)。Cox 比例风险模型确定 MΦ^高（风险比 [HR] = 2.02, 95%，p  = 0.032）、CD8^低（HR = 2.45，p  = 0.011）和肿瘤 PD-L1 表达（HR = 2.74，p  = 0.0061）作为潜在的风险因素。根据肿瘤细胞和肿瘤免疫微环境特征，pMMR CRC 患者可能会考虑针对免疫检查点疗法的 PD-L1–PD-1 和/或 CD47–SIRPA 轴。