|
|
外周血CD8+T细胞对肝细胞癌术后预后的价值研究
|
Abstract:
目的：外周免疫景观可能在肝细胞癌(HCC)的识别和控制中起关键作用。本研究旨在探讨外周血CD8+T细胞数量在预测肝细胞癌根治性肝切除术后预后中的价值。方法：选取2018年8月至2023年7月79例于我院行根治性肝切除术的初诊HCC患者作为研究对象，分析外周血CD8+T细胞数量对患者预后的预测价值。流式细胞术检测CD8+T细胞数量。结果：CD8+T细胞数量在早期复发和死亡患者中明显减少(p < 0.050)。多因素Cox回归分析显示CD8+T细胞数量是术后预后的独立影响因素(p < 0.050)。CD8+T细胞数量减少组的无复发生存期(RFS)和总生存期(OS)明显短于非减少组。结果经亚组分析证实。结论：外周血CD8+T细胞数量与HCC患者根治性肝切除术术后预后不良相关，可作为HCC患者术后新的预后指标。
Objective: The peripheral immune landscape may play a key role in determining hepatocellular carcinoma (HCC) recognition and control. This study aimed to examine the utility of peripheral blood CD8+T cells in predicting prognosis in HCC after curative hepatectomy. Methods: 79 newly diagnosed HCC patients from August 2018 to July 2023 were selected as research objects, we analyzed the prognostic value of peripheral blood CD8+T cells of HCC patients who underwent curative hepatectomy. The number of CD8+T cells was detected by flow cytometry. Results: The number of CD8+T cells was significantly decreased in patients who developed recurrence and death (all p < 0.050). Cox regression demonstrated that the number of CD8+T cells was an independent indicator for poor prognosis after hepatectomy (both p < 0.050). The recurrence-free survival (RFS) and overall survival (OS) in decrease group were significantly shorter than non-decrease group. The results were confirmed by the subgroup analysis. Conclusion: The number of CD8+T cells in peripheral blood is associated with dismal outcomes in HCC patients and can serve as a novel prognostic indicator for HCC patients after curative hepatectomy.
| [1] | Vogel, A., Cervantes, A., Chau, I., Daniele, B., Llovet, J.M., Meyer, T., et al. (2018) Hepatocellular Carcinoma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up. Annals of Oncology, 29, iv238-iv255. https://doi.org/10.1093/annonc/mdy308 |
| [2] | Llovet, J.M., Castet, F., Heikenwalder, M., Maini, M.K., Mazzaferro, V., Pinato, D.J., et al. (2021) Immunotherapies for Hepatocellular Carcinoma. Nature Reviews Clinical Oncology, 19, 151-172. https://doi.org/10.1038/s41571-021-00573-2 |
| [3] | Chan, T.A., Yarchoan, M., Jaffee, E., Swanton, C., Quezada, S.A., Stenzinger, A., et al. (2019) Development of Tumor Mutation Burden as an Immunotherapy Biomarker: Utility for the Oncology Clinic. Annals of Oncology, 30, 44-56. https://doi.org/10.1093/annonc/mdy495 |
| [4] | Goodman, A.M., Kato, S., Bazhenova, L., Patel, S.P., Frampton, G.M., Miller, V., et al. (2017) Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Molecular Cancer Therapeutics, 16, 2598-2608. https://doi.org/10.1158/1535-7163.mct-17-0386 |
| [5] | Shang, B., Liu, Y., Jiang, S. and Liu, Y. (2015) Prognostic Value of Tumor-Infiltrating FoxP3+ Regulatory T Cells in Cancers: A Systematic Review and Meta-Analysis. Scientific Reports, 5, Article No. 15179. https://doi.org/10.1038/srep15179 |
| [6] | Huang, A.C., Postow, M.A., Orlowski, R.J., Mick, R., Bengsch, B., Manne, S., et al. (2017) T-Cell Invigoration to Tumour Burden Ratio Associated with Anti-PD-1 Response. Nature, 545, 60-65. https://doi.org/10.1038/nature22079 |
| [7] | Blackburn, S.D., Shin, H., Haining, W.N., Zou, T., Workman, C.J., Polley, A., et al. (2008) Coregulation of CD8+ T Cell Exhaustion by Multiple Inhibitory Receptors during Chronic Viral Infection. Nature Immunology, 10, 29-37. https://doi.org/10.1038/ni.1679 |
| [8] | Postow, M.A., Callahan, M.K. and Wolchok, J.D. (2015) Immune Checkpoint Blockade in Cancer Therapy. Journal of Clinical Oncology, 33, 1974-1982. https://doi.org/10.1200/jco.2014.59.4358 |
| [9] | Watson, R.A., Tong, O., Cooper, R., Taylor, C.A., Sharma, P.K., de los Aires, A.V., et al. (2021) Immune Checkpoint Blockade Sensitivity and Progression-Free Survival Associates with Baseline CD8+ T Cell Clone Size and Cytotoxicity. Science Immunology, 6, eabj8825. https://doi.org/10.1126/sciimmunol.abj8825 |
| [10] | Tsilimigras, D.I., Bagante, F., Sahara, K., Moris, D., Hyer, J.M., Wu, L., et al. (2019) Prognosis after Resection of Barcelona Clinic Liver Cancer (BCLC) Stage 0, A, and B Hepatocellular Carcinoma: A Comprehensive Assessment of the Current BCLC Classification. Annals of Surgical Oncology, 26, 3693-3700. https://doi.org/10.1245/s10434-019-07580-9 |
| [11] | Zhang, J., Qin, S.D., Li, Y., Lu, F., Gong, W.F., Zhong, J.H., et al. (2022) Prognostic Significance of Combined α-Fetoprotein and CA19-9 for Hepatocellular Carcinoma after Hepatectomy. World Journal of Surgical Oncology, 20, Article No. 346. https://doi.org/10.1186/s12957-022-02806-9 |
| [12] | Xing, H., Jiang, X., Yang, C., Tan, B., Hu, J. and Zhang, M. (2023) High Expression of RPL27A Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma. World Journal of Surgical Oncology, 21, Article No. 209. https://doi.org/10.1186/s12957-023-03102-w |
| [13] | Tang, K., Seo, J., Tiu, B.C., Le, T.K., Pahalyants, V., Raval, N.S., et al. (2022) Association of Cutaneous Immune-Related Adverse Events with Increased Survival in Patients Treated with Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Therapy. JAMA Dermatology, 158, 189-193. https://doi.org/10.1001/jamadermatol.2021.5476 |
| [14] | Sendi, H., Yazdimamaghani, M., Hu, M., Sultanpuram, N., Wang, J., Moody, A.S., et al. (2022) Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis. Cancer Research, 82, 105-113. https://doi.org/10.1158/0008-5472.can-21-2269 |
| [15] | Lu, M., Wu, J., Hao, Z., Shang, Y., Xu, J., Nan, G., et al. (2018) Basolateral CD147 Induces Hepatocyte Polarity Loss by E‐Cadherin Ubiquitination and Degradation in Hepatocellular Carcinoma Progress. Hepatology, 68, 317-332. https://doi.org/10.1002/hep.29798 |
| [16] | Zheng, C., Zheng, L., Yoo, J., Guo, H., Zhang, Y., Guo, X., et al. (2017) Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing. Cell, 169, 1342-1356.e16. https://doi.org/10.1016/j.cell.2017.05.035 |
| [17] | Huang, Y., Jia, A., Wang, Y. and Liu, G. (2022) CD8+ T Cell Exhaustion in Anti‐Tumour Immunity: The New Insights for Cancer Immunotherapy. Immunology, 168, 30-48. https://doi.org/10.1111/imm.13588 |
| [18] | Dolina, J.S., Van Braeckel-Budimir, N., Thomas, G.D. and Salek-Ardakani, S. (2021) CD8+ T Cell Exhaustion in Cancer. Frontiers in Immunology, 12, Article 715234. https://doi.org/10.3389/fimmu.2021.715234 |
| [19] | Sun, R., Li, J., Lin, X., Yang, Y., Liu, B., Lan, T., et al. (2023) Peripheral Immune Characteristics of Hepatitis B Virus-Related Hepatocellular Carcinoma. Frontiers in Immunology, 14, Article 1079495. https://doi.org/10.3389/fimmu.2023.1079495 |
| [20] | Tumeh, P.C., Harview, C.L., Yearley, J.H., Shintaku, I.P., Taylor, E.J.M., Robert, L., et al. (2014) PD-1 Blockade Induces Responses by Inhibiting Adaptive Immune Resistance. Nature, 515, 568-571. https://doi.org/10.1038/nature13954 |
| [21] | Barsch, M., Salié, H., Schlaak, A.E., Zhang, Z., Hess, M., Mayer, L.S., et al. (2022) T-Cell Exhaustion and Residency Dynamics Inform Clinical Outcomes in Hepatocellular Carcinoma. Journal of Hepatology, 77, 397-409. https://doi.org/10.1016/j.jhep.2022.02.032 |
| [22] | Wang, X., He, Q., Shen, H., Xia, A., Tian, W., Yu, W., et al. (2019) TOX Promotes the Exhaustion of Antitumor CD8+ T Cells by Preventing PD1 Degradation in Hepatocellular Carcinoma. Journal of Hepatology, 71, 731-741. https://doi.org/10.1016/j.jhep.2019.05.015 |
