The role of the immunoescape in colorectal cancer liver metastasis.
The role of the immunoescape in colorectal cancer liver metastasis.
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DOI：
10.1371/journal.pone.0259940
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Shimada M
中科院分区：
文献类型：
--
作者：
Takasu C;Yamashita S;Morine Y;Yoshikawa K;Tokunaga T;Nishi M;Kashihara H;Yoshimoto T;Shimada M
程序性死亡1（PD-1）和程序性死亡配体1（PD-L1）的表达表明抗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）的治疗效果作用不大。本研究探讨了免疫分子对 CRLM 预后的影响。我们招募了 71 名接受 CRC 根治性切除术的 CRLM 患者。我们使用免疫组织化学分析转移性肿瘤中 PD-1、PD-L1、吲哚胺吡咯 2,3-双加氧酶 (IDO) 和 CD163（肿瘤相关巨噬细胞 [TAM] 的标记物）的表达。免疫分子 PD-1、PD-L1、IDO 和 TAM 分别在 32.3%、47.8%、45.0% 和 47.9% 的转移性 CRC 样本中表达。免疫分子阳性组的 5 年总体生存率显着优于阴性组（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）。多变量分析显示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）作为独立的预后指标。转移中的 PD-1 和 TAM 与较小的肿瘤等侵袭性较低的特征相关。此外，TAM 与 PD-1 表达 (p = 0.011)、PD-L1 表达 (p = 0.024) 呈显着正相关，并倾向于与 IDO 表达相关 (p = 0.078)。 CRLM 中的 PD-1、PD-L1、IDO 和 TAM 与 CRC 患者的侵袭性特征较低和预后较好相关，表明适应性抗肿瘤免疫与免疫耐受。因此，这些分子可以作为 CRLM 的预后标志物。
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.
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DOI：
10.1186/s12964-018-0262-x
发表时间：
2018-09-04
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Feng R;Morine Y;Ikemoto T;Imura S;Iwahashi S;Saito Y;Shimada M
通讯作者：
Shimada M
影响因子：
11.5
作者：
Brandacher, G;Perathoner, A;Amberger, A
通讯作者：
Amberger, A
影响因子：
2.5
作者：
Douaiher, Jeffrey;Ravipati, Advaitaa;Are, Chandrakanth
通讯作者：
Are, Chandrakanth
影响因子：
64.8
作者：
GERSHON, RK;MOKYR, MB;MITCHELL, MS
通讯作者：
MITCHELL, MS
影响因子：
3.7
作者：
Katz SC;Bamboat ZM;Maker AV;Shia J;Pillarisetty VG;Yopp AC;Hedvat CV;Gonen M;Jarnagin WR;Fong Y;D'Angelica MI;DeMatteo RP
通讯作者：
DeMatteo RP