研究动态
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从AtezoT RIBE研究中剖析肿瘤淋巴细胞浸润,预测免疫检查点抑制剂治疗转移性结直肠癌的益处。

Dissecting tumor lymphocyte infiltration to predict benefit from immune-checkpoint inhibitors in metastatic colorectal cancer: lessons from the AtezoT RIBE study.

发表日期:2023 Apr
作者: Roberto Moretto, Daniele Rossini, Aurélie Catteau, Carlotta Antoniotti, Mirella Giordano, Alessandra Boccaccino, Clara Ugolini, Agnese Proietti, Veronica Conca, Alboukadel Kassambara, Filippo Pietrantonio, Lisa Salvatore, Sara Lonardi, Stefano Tamberi, Emiliano Tamburini, Anello Marcello Poma, Jacques Fieschi, Gabriella Fontanini, Gianluca Masi, Jérôme Galon, Chiara Cremolini
来源: Journal for ImmunoTherapy of Cancer

摘要:

肿瘤免疫细胞影响免疫检查点抑制剂(ICIs)的功效,许多努力旨在确定肿瘤免疫微环境的特征,以预测pMMR /微卫星稳定(MSS)转移性结直肠癌(mCRC)中ICIs的受益。我们通过评估AtezoTRIBE研究入组mCRC患者的肿瘤样本中的肿瘤浸润淋巴细胞(TILs),免疫得分,免疫得分-IC和程序性死亡配体-1(PD-L1)表达,表征了肿瘤免疫细胞浸润,并旨在评估这些特征的预后和预测价值。218名入组患者中,成功测试了181个(83%),77个(35%),157个(72%)和162个(74%)规格,TILs,免疫得分,免疫得分- IC和PD-L1表达分别为69(38%),45(58%),50(32%)和21(13%)。观察到TILs与免疫得分或免疫得分-IC的一致性很差(Cohen的K <0.20)。在pMMR人群中,与免疫得分低(16.4 vs 12.2个月; HR:0.55,95%CI:0.30至0.99; p = 0.049)和免疫得分-IC低(14.8 vs 11.5个月; HR:0.55,95%CI:0.35至0.85; p = 0.007)分组相比,免疫得分高和免疫得分-IC高组报告了更长的无进展生存(PFS),并且存在治疗方案和免疫得分-IC之间的显著交互作用(p交互:0.006),并有免疫得分的趋势(p交互:0.13)。根据TILs和PD-L1表达,未显示出PFS差异。总体人群报告了一致的结果。通过免疫得分-IC或免疫得分的数字评估,鉴定了pMMR mCRC患者的亚组,在ICIs的前期治疗中获得了更多的益处。免疫得分-IC是ICIs受益的最有前途的预测因素。©作者(或其雇主)2023。在CC BY-NC下允许再次使用。不进行商业再利用。由BMJ出版。
Tumor immune cells influence the efficacy of immune-checkpoint inhibitors (ICIs) and many efforts aim at identifying features of tumor immune microenvironment able to predict benefit from ICIs in proficient mismatch repair (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC).We characterized tumor immune cell infiltrate, by assessing tumor-infiltrating lymphocytes (TILs), Immunoscore, Immunoscore-IC, and programmed death ligand-1 (PD-L1) expression in tumor samples of patients with mCRC enrolled in the AtezoTRIBE study, a phase II randomized trial comparing FOLFOXIRI/bevacizumab/atezolizumab to FOLFOXIRI/bevacizumab, with the aim of evaluating the prognostic and predictive value of these features.Out of 218 patients enrolled, 181 (83%), 77 (35%), 157 (72%) and 162 (74%) specimens were successfully tested for TILs, Immunoscore, Immunoscore-IC and PD-L1 expression, respectively, and 69 (38%), 45 (58%), 50 (32%) and 21 (13%) tumors were classified as TILs-high, Immunoscore-high, Immunoscore-IC-high and PD-L1-high, respectively. A poor agreement was observed between TILs and Immunoscore or Immunoscore-IC (K of Cohen <0.20). In the pMMR population, longer progression-free survival (PFS) was reported for Immunoscore-high and Immunoscore-IC-high groups compared with Immunoscore-low (16.4 vs 12.2 months; HR: 0.55, 95% CI: 0.30 to 0.99; p=0.049) and Immunoscore-IC-low (14.8 vs 11.5 months; HR: 0.55, 95% CI: 0.35 to 0.85; p=0.007), respectively, with a significant interaction effect between treatment arms and Immunoscore-IC (p for interaction: 0.006) and a trend for Immunoscore (p for interaction: 0.13). No PFS difference was shown according to TILs and PD-L1 expression. Consistent results were reported in the overall population.The digital evaluation of tumor immune cell infiltrate by means of Immunoscore-IC or Immunoscore identifies the subset of patients with pMMR mCRC achieving more benefit from the addition of the anti-PD-L1 to the upfront treatment. Immunoscore-IC stands as the most promising predictor of benefit from ICIs.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.