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Abstract：
BACKGROUND: Tissue-resident memory CD103+CD8+ T cells (CD103+CD8+ TRMs) are important components of anti-tumor immunity. However, the significance of CD103+CD8+ TRMs in colorectal cancer (CRC) and their advantages remain unclear.
METHODS: Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.
RESULTS: In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects.
CONCLUSIONS: We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.
METHODS: Clinical data and specimens were used to evaluate the significance of CD103+CD8+ TRMs in CRC. A mouse subcutaneous tumorigenesis model and colony-formation assay were conducted to evaluate the anti-tumor effects of CD103+CD8+ TRMs. Finally, the infiltration density and function of CD103+CD8+ TRMs in the tumors were evaluated using flow cytometry.
RESULTS: In this study, we showed that highly infiltrated CD103+CD8+ TRMs were associated with earlier clinical stage and negative VEGF expression in CRC patients and predicted a favorable prognosis for CRC/CRC liver metastases patients. Interestingly, we also found that CD103+CD8+ TRMs may have predictive potential for whether CRC develops liver metastasis in CRC. In addition, we found a positive correlation between the ratio of the number of α-SMA+ vessels to the sum of the number of α-SMA+ and CD31+ vessels in CRC, and the infiltration level of CD103+CD8+ TRMs. In addition, anti-angiogenic therapy promoted infiltration of CD103+CD8+ TRMs and enhanced their ability to secrete interferon (IFN)-γ, thus further improving the anti-tumor effect. Moreover, in vivo experiments showed that compared with peripheral blood CD8+ T cells, CD103+CD8+ TRMs infused back into the body could also further promote CD8+ T cells to infiltrate the tumor, and they had a stronger ability to secrete IFN-γ, which resulted in better anti-tumor effects.
CONCLUSIONS: We demonstrated that CD103+CD8+ TRMs have the potential for clinical applications and provide new ideas for combined anti-tumor therapeutic strategies, such as anti-tumor angiogenesis therapy and CAR-T combined immunotherapy.
摘要：
背景：组织内记忆CD103+CD8+T细胞（CD103+CD8+TRMs）是抗肿瘤免疫的重要组成部分。然而,CD103+CD8+TRMs在结直肠癌(CRC)中的意义及其优势尚不清楚.
方法：使用临床数据和标本评估CD103+CD8+TRMs在CRC中的意义。通过小鼠皮下肿瘤发生模型和集落形成实验来评估CD103CD8TRMs的抗肿瘤作用。最后，使用流式细胞术评估肿瘤中CD103CD8TRMs的浸润密度和功能。
结果：在这项研究中，我们发现,在CRC患者中,高度浸润的CD103+CD8+TRMs与早期临床分期和VEGF阴性表达相关,并预测CRC/CRC肝转移患者的预后良好.有趣的是,我们还发现,CD103+CD8+TRMs可能对CRC中是否发生肝转移具有预测潜力.此外,我们发现CRC中α-SMA+血管数与α-SMA+和CD31+血管数之和呈正相关,和CD103+CD8+TRMs的浸润水平。此外，抗血管生成治疗促进CD103+CD8+TRMs的浸润并增强其分泌干扰素（IFN）-γ的能力，从而进一步提高抗肿瘤效果。此外，体内实验表明，与外周血CD8+T细胞相比，CD103+CD8+TRMs输注回体内还可进一步促进CD8+T细胞浸润肿瘤，它们分泌IFN-γ的能力更强，从而产生更好的抗肿瘤效果。
结论：我们证明了CD103+CD8+TRMs具有临床应用的潜力，并为联合抗肿瘤治疗策略提供了新思路。如抗肿瘤血管生成治疗和CAR-T联合免疫疗法。
方法：使用临床数据和标本评估CD103+CD8+TRMs在CRC中的意义。通过小鼠皮下肿瘤发生模型和集落形成实验来评估CD103CD8TRMs的抗肿瘤作用。最后，使用流式细胞术评估肿瘤中CD103CD8TRMs的浸润密度和功能。
结果：在这项研究中，我们发现,在CRC患者中,高度浸润的CD103+CD8+TRMs与早期临床分期和VEGF阴性表达相关,并预测CRC/CRC肝转移患者的预后良好.有趣的是,我们还发现,CD103+CD8+TRMs可能对CRC中是否发生肝转移具有预测潜力.此外,我们发现CRC中α-SMA+血管数与α-SMA+和CD31+血管数之和呈正相关,和CD103+CD8+TRMs的浸润水平。此外，抗血管生成治疗促进CD103+CD8+TRMs的浸润并增强其分泌干扰素（IFN）-γ的能力，从而进一步提高抗肿瘤效果。此外，体内实验表明，与外周血CD8+T细胞相比，CD103+CD8+TRMs输注回体内还可进一步促进CD8+T细胞浸润肿瘤，它们分泌IFN-γ的能力更强，从而产生更好的抗肿瘤效果。
结论：我们证明了CD103+CD8+TRMs具有临床应用的潜力，并为联合抗肿瘤治疗策略提供了新思路。如抗肿瘤血管生成治疗和CAR-T联合免疫疗法。
