Hepato-Gastroenterology Department, CHU Poitiers, Poitiers, France.
Université de Poitiers, CHU Poitiers, INSERM, PRODICET, Poitiers, France.
Front Immunol. 2021 Oct 18;12:750407. doi: 10.3389/fimmu.2021.750407. eCollection 2021.
Incidence of brain metastases has increased in patients with colorectal cancer (CRC) as their survival has improved. CD3 T-cells and, lately, DGMate (DiGital tuMor pArameTErs) score, have been identified as prognostic factors in locally advanced CRC. Until now, there is no data concerning the prognostic value of these markers in patients with CRC-derived brain metastases. All consecutive patients with CRC-derived brain metastases diagnosed between 2000 and 2017 were retrospectively included. Staining for CD3, CD8, PD-1, PD-L1 and DGMate analyses were performed using tissue micro-array from primary tumors and, if available, brain metastases. All in all, 83 patients were included with 80 primary tumor samples and 37 brain metastases samples available. CD3 and CD8 T-cell infiltration was higher in primary tumors compared to brain metastases. We observed a significant higher DGMate score in rectal tumors compared to colon tumors (p=0.03). We also noted a trend of higher CD3 T-cell infiltration in primary tumors when brain metastases were both supra and subtentorial compared to brain metastases that were only subtentorial or supratentorial (p=0.36 and p=0.03, respectively). No correlation was found between CD3 or CD8 infiltration or DGMate score in primary tumors or brain metastases and overall survival (OS) in the overall population. In patients with rectal tumors, a high DGMate score in brain metastases was associated with longer OS (13.4 ± 6.1 months versus 6.1 ± 1.4 months, p=0.02). High CD3 T-cell infiltration in brain metastases was associated with lower OS in patients with supratentorial brain metastases (9.8 ± 3.3 months versus 16.7 ± 5.9 months, p=0.03). PD-L1 overexpression was rare, both in primary tumors and brain metastases, but PD-L1 positive primary tumors were associated with worse OS (p=0.01). In contrast to breast and lung cancer derived brain metastases, CD3 and CD8 infiltration and DGMate score are not major prognostic factors in patients with CRC-derived brain metastases.
结直肠癌（CRC）患者的生存时间延长，导致脑转移的发生率增加。CD3 T 细胞和最近的 DGMate（数字肿瘤参数）评分已被确定为局部晚期 CRC 的预后因素。到目前为止，尚无这些标志物在 CRC 脑转移患者中的预后价值的数据。所有 2000 年至 2017 年间诊断为 CRC 脑转移的连续患者均被回顾性纳入。使用原发性肿瘤和（如有）脑转移灶的组织微阵列进行 CD3、CD8、PD-1、PD-L1 染色和 DGMate 分析。总共纳入了 83 例患者，其中 80 例原发性肿瘤样本和 37 例脑转移样本可用。与脑转移相比，原发性肿瘤中 CD3 和 CD8 T 细胞浸润更高。我们观察到直肠肿瘤的 DGMate 评分明显高于结肠肿瘤（p=0.03）。我们还注意到，当脑转移同时位于幕上和幕下时，原发性肿瘤中 CD3 T 细胞浸润较高，而当脑转移仅位于幕下或幕上时，这种趋势更为明显（分别为 p=0.36 和 p=0.03）。在整个人群中，原发性肿瘤或脑转移灶中 CD3 或 CD8 浸润或 DGMate 评分与总生存期（OS）之间均无相关性。在直肠肿瘤患者中，脑转移灶中 DGMate 评分高与 OS 延长相关（13.4±6.1 个月与 6.1±1.4 个月，p=0.02）。幕上脑转移患者脑转移灶中 CD3 T 细胞浸润较高与 OS 较低相关（9.8±3.3 个月与 16.7±5.9 个月，p=0.03）。PD-L1 过表达在原发性肿瘤和脑转移灶中均罕见，但 PD-L1 阳性的原发性肿瘤与较差的 OS 相关（p=0.01）。与乳腺癌和肺癌脑转移不同，CD3 和 CD8 浸润和 DGMate 评分不是 CRC 脑转移患者的主要预后因素。
