肿瘤组织T细胞亚群与结直肠癌术后化疗疗效的相关性

摘要

探讨肿瘤组织T细胞亚群与结直肠癌患者术后化疗疗效的相关性。选取2021年1月—2024年5月于保定市第二中心医院进行化疗的95例结直肠癌患者为研究对象，化疗完成后参照RECIST疗效评价标准评估患者化疗疗效，将发生疾病进展的患者纳入进展组（n=54），未出现疾病进展的患者纳入未进展组（n=39），2例未完成化疗不计入组内。采用免疫组织化学方法测量术后CD3 ⁺T细胞、CD4 ⁺T细胞、CD8 ⁺T细胞、FoxP3 ⁺Tregs细胞表达状况，通过多因素Logistic分析影响结直肠癌术后化疗疗效的影响因素，采用受试者工作特征（ROC）曲线评估肿瘤T细胞亚群对结直肠癌术后化疗疗效的预测能力。两组CEA水平及CD3 ⁺、CD4 ⁺、CD8 ⁺、FoxP3 ⁺Tregs等T淋巴细胞亚群的比例，差异均有统计学意义（P<0.05）。单因素及多因素Logistic回归分析证实，CD8 ⁺T细胞（OR=0.394，P=0.003）与FoxP3 ⁺Tregs细胞（OR=0.257，P=0.001）是结直肠癌术后化疗疗效的保护因素。ROC曲线显示，CD8 ⁺T细胞（AUC=0.901，95%CI：0.837~0.966）和FoxP3 ⁺Tregs细胞（AUC=0.940，95%CI：0.892~0.989）能够预测结直肠癌术后化疗疗效（均P<0.05）。CD8 ⁺T细胞、Foxp3 ⁺Tregs细胞水平与结直肠癌术后化疗疗效密切相关，且可预测结直肠癌患者术后化疗疗效。

关键词

结直肠癌 / 化疗疗效 / T细胞亚群 / 特异性转录因子叉头状转录因子P3

参考文献

[1] Thomas CE , Lin Y , Kim M , et al. Characterization of Additive gene—environment interactions for colorectal cancer risk[J]. Epidemiology, 2025, 36(1): 126-138. DOI: 10.1097/EDE.0000000000001795.

[2] Chen Z , Song W , Shu XO , et al. Novel insights into genetic susceptibility for colorectal cancer from transcriptome—wide association and functional investigation[J]. J Natl Cancer Inst, 2024, 116(1): 127-137. DOI: 10.1093/jnci/djad178.

[3] Hickson M , Papoutsakis C , Madden AM . Nature of the evidence base and approaches to guide nutrition interventions for individuals: a position paper from the Academy of Nutrition Sciences[J]. Br J Nutr, 2024, 131(10): 1754-1773. DOI: 10.1017/S0007114524000291.

[4] 杨贵淞， 陈焕杰， 马贵亮， 等 . FOXQ1通过促进p53去乙酰化抑制结直肠癌DNA损伤性凋亡的机制研究[J]. 中国现代普通外科进展， 2025， 28（4）： 266-270. DOI: 10.3969/j.issn.1009—9905.2025.04.003.

[5] Niu X , You Q , Hou K , et al. Autophagy in cancer development, immune evasion, and drug resistance[J]. Drug Resist Updat, 2025, 78: 101170. DOI: 10.1016/j.drup.2024.101170.

[6] Liu X , Liu D , Tan C , et al. Systemic immune profiling analysis identifying M2—TAM related genes predicted colon cancer prognosis and chemotherapy responses[J]. Medicine (Baltimore), 2024, 103: e40979. DOI: 10.1097/MD.0000000000040979.

[7] Zhang JG , Pan SK , Chen J , et al. Immunostimulatory properties of chemotherapy in breast cancer: from immunogenic modulation mechanisms to clinical practice[J]. Front Immunol, 2021, 12: 819405. DOI: 10.3389/fimmu.2021.819405.

[8] Anaya DA , Dogra P , Wang ZH , et al. A mathematical model to estimate chemotherapy concentration at the tumor—site and predict therapy response in colorectal cancer patients with liver metastases[J]. Cancers (Basel), 2021, 13(3): 444. DOI: 10.3390/cancers13030444.

[9] Ferrara R , Imbimbo M , Malouf R , et al. Single or combined immune checkpoint inhibitors compared to first—line platinum—based chemotherapy with or without bevacizumab for people with advanced non—small cell lung cancer[J]. Cochrane Database Syst Rev, 2020, 2020(12): CD013257. DOI: 10.1002/14651858.CD013257.pub2.

[10] 中华人民共和国国家卫生健康委员会 . 中国结直肠癌诊疗规范（2020年版）[J]. 中华外科杂志， 2020， 58（8）： 561-585. DOI: 10.3760/cma.j.cn112139—20200518—00390.

[11] 蒲文吉， 苏晓晔， 冯玲玲， 等 . 新辅助免疫治疗在局部晚期直肠癌中应用循证证据[J]. 中国肿瘤临床， 2024， 51（9）： 472-479. DOI: 10.12354/j.issn.1000—8179.2024.20240443.

[12] Chang C , Cai Z , Cheng K , et al. Efficacy and safety of S—1 plus oxaliplatin combined with apatinib and camrelizumab as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction adenocarcinoma: a protocol for a single—arm phase II trial[J]. Updates Surg, 2025, 77(1): 165-174. DOI: 10.1007/s13304—024—02052—6.

[13] Liu H , Dong A , Rasteh AM , et al. Identification of the novel exhausted T cell CD8 ⁺ markers in breast cancer [J]. Sci Rep, 2024, 14(1): 19142. DOI: 10.1016/j.bioorg.2020.104452.

[14] Sinicrope FA , Nelson GD , Saberzadeh—Ardestani B , et al. Use of deep learning to evaluate tumor microenvironmental features for prediction of colon cancer recurrence[J]. Cancer Res Commun, 2024, 4(5): 1344-1350. DOI: 10.1158/2767—9764.CRC—24—0031.

[15] Cinier J , Hubert M , Besson L , et al. Recruitment and expansion of tregs cells in the tumor environment: how to target the?[J]. Cancers (Basel), 2021, 13(8): 1850. DOI: 10.3390/cancers13081850.

[16] Truong NTH , Gargett T , Brown MP , et al. Effects of chemotherapy agents on circulating leukocyte populations: potential implications for the success of CAR—T cell therapies[J]. Cancers (Basel), 2021, 13(9): 2225. DOI: 10.3390/cancers13092225.

[17] Lan H , Xu S , Li H , et al. T cell aging: an important target for perioperative immunomodulation[J]. Clin Interv Aging, 2025, 20: 537-557. DOI: 10.2147/CIA.S519438.

[18] Schoumacher C , Derangère V , Gaudillière—Le Dain G , et al. CD3—CD8 immune score associated with a clinical score stratifies PDAC prognosis regardless of adjuvant or neoadjuvant chemotherapy[J]. Oncoimmunology, 2024, 13(1): 2294563. DOI: 10.1080/2162402X.2023.2294563.

[19] Jeon SH , Lim YJ , Koh J , et al. A radiomic signature model to predict the chemoradiation—induced alteration in tumor—infiltrating CD8 ⁺ cells in locally advanced rectal cancer [J]. Radiother Oncol, 2021, 162: 124-131. DOI: 10.1016/j.radonc.2021.07.004.

[20] Li X , Zhou HD , Huang WW , et al. Retrospective analysis of the efficacy of adjuvant cytokine—induced killer cell immunotherapy combined with chemotherapy in colorectal cancer patients after surgery[J]. Clin Transl Immunology, 2022, 11(1): 1368. DOI: 10.1002/cti2.1368.

[21] Wang XG , Waschke BC , Woolaver RA , et al. MHC class I—independent activation of virtual memory CD8 T cells induced by chemotherapeutic agent—treated cancer cells[J]. Cell Mol Immunol, 2021, 18(3): 723-734. DOI: 10.1038/s41423—020—0463—2.

[22] 李云康， 赵立仙， 潘云 . 肿瘤相关高内皮微静脉在肿瘤中的作用及其临床意义[J]. 中国肿瘤生物治疗杂志， 2025， 32（1）： 107-114. DOI: 10.3872/j.issn.1007—385x.2025.01.015.

[23] Hu G , Li Z , Wang S . Tumor—infiltrating FoxP3(+) Tregs predict favorable outcome in colorectal cancer patients: A meta—analysis[J]. Oncotarget, 2017, 8(43): 75361-75371. DOI: 10.18632/oncotarget.17722.

[24] Sun Y , Wang Y , Lu F , et al. The prognostic values of FOXP3(+) tumor—infiltrating T cells in breast cancer: a systematic review and meta—analysis[J]. Clin Transl Oncol, 2023, 25(6): 1830-1843. DOI: 10.1007/s12094—023—03080—1.

[25] Xu PP , Fan W , Zhang Z , et al. The Clinicopathological and prognostic implications of foxp3+ regulatory t cells in patients with colorectal cancer: a meta—analysis[J]. Front Physiol, 2017, 8: 950. DOI: 10.3389/fphys.2017.00950.

[26] Li FX , Zhao Y , Wei LJ , et al. Tumor—infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer[J]. Cancer Biol Ther, 2018, 19(8): 695-705. DOI: 10.1080/15384047.2018.1450116.

[27] Bernal—Estévez DA , García O , Sánchez R , et al. Monitoring the responsiveness of T and antigen presenting cell compartments in breast cancer patients is useful to predict clinical tumor response to neoadjuvant chemotherapy[J]. BMC Cancer, 2018, 18: 77. DOI: 10.1186/s12885—017—3982—1.

[28] Kang J , Sun M , Chang Y , et al. Butyrate ameliorates colorectal cancer through regulating intestinal microecological disorders[J]. Anti—cancer drugs, 2023, 34(2): 227-237. DOI: 10.1097/CAD.0000000000001413.

基金资助

河北省医学科学研究课题计划项目(20230103)