Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy.
Eur J Cancer. 2020 Aug;135:78-88. doi: 10.1016/j.ejca.2020.04.045. Epub 2020 Jun 15.
Immune-contexture of tumour microenvironment (TME) influences prognosis of colorectal cancer (CRC) patients and can be altered by cytotoxic and targeted agents. Limited data are available regarding the immune-TME of CRC after treatment.
An extensive immunohistochemistry evaluation of immunological parameters on tumour cells and TME of colorectal liver metastases from 106 patients who underwent secondary resection, after receiving triplets FOLFOXIRI (5-fluorouracil, oxaliplatin and irinotecan) or COI (capecitabine, oxaliplatin and irinotecan) plus bevacizumab (N = 59) or cetuximab (N = 47) in five first-line no-profit clinical trials was performed.
No substantial differences were reported in immunological parameters according to administered targeted agent, RAS/BRAF mutational status and histopathological or Response Evaluation Criteria in Solid Tumours response. Stromal expression of Cyclooxygenase-2 (COX-2) (p = 0.002), Human leukocyte antigen (HLA) (p = 0.003) and Programmed cell death protein 1 (PD1) (p = 0.002) were independent prognostic factors for longer relapse-free survival (RFS) at multivariate analysis with a positive trend for post-resection overall survival (OS). Patients whose metastases expressed stromal COX-2, HLA and PD1 (inflamed-score positive) reported longer RFS (25.5 versus 9.8 months; p < 0.001) and post-resection OS (64.3 versus 37.7 months; p = 0.003) as compared with others. In addition, patients with higher expression of CD4 and CD8 T-cells in tumour core and invasive margin (CD4/CD8-score) showed a better post-resection OS (not-reached versus 41.6 months; p = 0.032). A combined score of inflamed-score and CD4/CD8-score (combo-score) showed a clear prognostic role.
The present study emphasises the role of immune-TME as independent predictor of survival in patients resected after triplets plus biologic. Inflamed-, CD4/C8- and combo-scores should be confirmed as prognostic factors in further studies.
肿瘤微环境（TME）的免疫结构影响结直肠癌（CRC）患者的预后，并且可以通过细胞毒性和靶向药物进行改变。关于治疗后 CRC 的免疫-TME，目前仅有有限的数据。
对 106 例接受三联 FOLFOXIRI（氟尿嘧啶、奥沙利铂和伊立替康）或 COI（卡培他滨、奥沙利铂和伊立替康）加贝伐单抗（N=59）或西妥昔单抗（N=47）治疗后行二次切除术的结直肠癌肝转移患者的肿瘤细胞和 TME 进行广泛的免疫组织化学评估，这些患者来自五项非营利性临床试验。
根据靶向药物、RAS/BRAF 突变状态以及组织病理学或实体瘤反应评估标准，免疫参数无明显差异。基质表达环氧化酶-2（COX-2）（p=0.002）、人类白细胞抗原（HLA）（p=0.003）和程序性死亡蛋白 1（PD1）（p=0.002）是多因素分析中与更长无复发生存期（RFS）相关的独立预后因素，并且与术后总生存期（OS）的阳性趋势相关。转移灶表达基质 COX-2、HLA 和 PD1（炎症评分阳性）的患者 RFS（25.5 个月与 9.8 个月；p<0.001）和术后 OS（64.3 个月与 37.7 个月；p=0.003）均较长。此外，肿瘤核心和侵袭边缘中 CD4 和 CD8 T 细胞表达较高（CD4/CD8 评分）的患者术后 OS 更好（未达到与 41.6 个月；p=0.032）。炎症评分和 CD4/CD8 评分的联合评分（组合评分）显示出明确的预后作用。
本研究强调了免疫-TME 作为接受三联加生物治疗后切除患者的独立生存预测因子的作用。炎症评分、CD4/CD8 评分和组合评分应在进一步研究中确认为预后因素。
