Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor-Node-Metastasis Stages.

IF 3.3 Q3 ONCOLOGY Cancer research communications Pub Date : 2024-11-01 DOI:10.1158/2767-9764.CRC-24-0270
Hao Kong, Qingxin Yang, Chunwei Wu, Xiangji Wu, Xinrui Yan, Li-Bin Huang, Lu Chen, Zong-Guang Zhou, Ping Wang, Hong Jiang
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Abstract

Significance: The identification of specific spatial patterns of immune checkpoint expression that correlate with overall survival in patients with colon cancer suggests a potential prognostic tool for risk stratification and treatment selection. These findings pave the way for the development of novel therapeutic strategies to enhance antitumor immune responses.

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免疫检查点的空间背景是可切除结直肠癌患者总生存期的预测因素,与标准 TNM 分期无关。
虽然免疫检查点阻断(ICB)疗法在一小部分微卫星不稳定性(MSI-H)较高的结直肠癌患者中显示出了良好的疗效,但大多数结直肠癌患者对 ICB 疗法并无反应。免疫疗法在癌症治疗中取得成功的主要障碍是肿瘤浸润淋巴细胞(TILs)的耗竭。阐明肿瘤微环境中免疫检查点的空间组织可为开发新型预后工具和治疗策略铺平道路,从而增强抗肿瘤免疫反应。为了明确结直肠肿瘤微环境(TME)中肿瘤浸润淋巴细胞(TILs)的空间和功能多样性,我们进行了多重 IHC 检测 TILs 在 TME 中的衰竭情况(PD-1 和 TIM-3(T 细胞免疫球蛋白和含粘蛋白域蛋白 3)的表达,它们是 T 细胞衰竭的主要生物标记物),并对 CRC 预后与 TME 特征之间的相关性进行了拉索-考克斯分析。为了验证概念,我们在人类 CRC 的 CT26 皮下肿瘤模型中进一步评估了 TIM-3 和 PD-1 双阻断对 CRC 的抗肿瘤疗效。我们发现,PD-1 和 TIM-3 的空间背景成功预测了 CRC 患者的总生存期,而与 TNM 分期无关。小鼠肿瘤模型中 PD-1 和 TIM-3 的双重靶向抑制了肿瘤的进展并减少了 T 细胞的耗竭,这为改善 CRC 的临床治疗提供了一种潜在的策略。
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