The Expression of Immune Checkpoint Receptors and Ligands in the Colorectal Cancer Tumor Microenvironment
The Expression of Immune Checkpoint Receptors and Ligands in the Colorectal Cancer Tumor Microenvironment
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DOI：
10.21873/anticanres.15303
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发表时间：
2021-10-01
影响因子：
2
通讯作者：
Kono, Koji
中科院分区：
文献类型：
--
作者：
Neupane, Prajwal;Mimura, Kosaku;Kono, Koji
背景/目的：免疫检查点抑制剂在结直肠癌（CRC）中的有限疗效可能是由于免疫抑制机制，包括肿瘤微环境中抑制性免疫检查点引起的T细胞耗竭。材料与方法：我们通过流式细胞术和免疫组织化学研究了肿瘤浸润性T细胞上抑制性免疫检查点受体及其肿瘤细胞上配体的表达状态，使用CRC的切除标本。结果如下：流式细胞术分析表明，TIM-3、TIGIT和PD-1在肿瘤浸润性CD 4+（8.3%、56.0%、26.1%）和CD 8 + T细胞（8.2%、51.6%、23.5%）上表达，并且CRC细胞大量表达PD-L1、CEACAM-1和CD 155（2.2%、77.0%、46.8%）。免疫组化分析显示，PD-L1、CEACAM-1和CD 155的肿瘤比例评分分别为42.4%、54.2%和52.1%。结论：PD-1、TIM-3和TIGIT轴可能降低CRC肿瘤微环境中的T细胞功能。
Background/Aim: The limited efficacy of immune checkpoint inhibitors in colorectal cancer (CRC) is likely due to immunosuppressive mechanisms including T cell exhaustion caused by inhibitory immune checkpoints in the tumor microenvironment. Materials and Methods: We investigated the expression status of the inhibitory immune checkpoint receptors on tumor-infiltrating T cells and their ligands on tumor cells by flow cytometry and immunohistochemistry, using surgically-resected specimens of CRC. Results: Flow cytometry analysis indicated that TIM-3, TIGIT, and PD-1 were expressed on tumor-infiltrating CD4+ (8.3%, 56.0%, 26.1%) and CD8+ T cells (8.2%, 51.6%, 23.5%), and CRC cells abundantly expressed PD- L1, CEACAM-1, and CD155 (2.2%, 77.0%, 46.8%). Immunohistochemical analysis revealed that the tumor proportional score of PD-L1, CEACAM-1, and CD155 was 42.4%, 54.2%, and 52.1%, respectively. Conclusion: PD-1, TIM-3, and TIGIT axes may reduce T cell function in the CRC tumor microenvironment.