Department of Surgery, Tokushima University, Tokushima, Japan.
PLoS One. 2021 Nov 19;16(11):e0259940. doi: 10.1371/journal.pone.0259940. eCollection 2021.
The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.
程序性死亡受体 1(PD-1)和程序性死亡配体 1(PD-L1)的表达预示着抗 PD-1/PD-L1 治疗在结直肠癌(CRC)中的疗效,但对于监测 CRC 肝转移(CRLM)的治疗效果则不太有用。本研究探讨了免疫分子对 CRLM 预后的影响。我们纳入了 71 例接受 CRC 根治性切除术的 CRLM 患者。我们使用免疫组织化学方法分析了转移性肿瘤中 PD-1、PD-L1、吲哚胺 2,3-双加氧酶(IDO)和 CD163(肿瘤相关巨噬细胞[TAMs]的标志物)的表达。在转移性 CRC 样本中,分别有 32.3%、47.8%、45.0%和 47.9%的样本表达免疫分子 PD-1、PD-L1、IDO 和 TAMs。与免疫分子阳性组相比,5 年总生存率显著提高(PD-1:87.7%比 53.2%,p=0.023;PD-L1:82.4%比 42.3%,p=0.007;IDO:80.7%比 43.5%,p=0.007;TAMs:82.6%比 48.0%,p=0.005)。多因素分析显示,PD-1 表达(p=0.032,风险比:0.19)、IDO 表达(p=0.049,风险比:0.37)和肿瘤分化(p<0.001,风险比:0.02)是独立的预后指标。转移灶中的 PD-1 和 TAMs 与较小的肿瘤等侵袭性特征相关。此外,TAMs 与 PD-1 表达(p=0.011)、PD-L1 表达(p=0.024)呈正相关,且与 IDO 表达呈正相关趋势(p=0.078)。CRLM 中的 PD-1、PD-L1、IDO 和 TAMs 与患者 CRC 的侵袭性特征和更好的预后相关,提示适应性抗肿瘤免疫与免疫耐受相关。这些分子因此可能成为 CRLM 的预后标志物。
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