1.广西中医药大学附属国际壮医医院壮瑶医药研究实验室,南宁;530201
2.南宁市第一人民医院(广西医科大学第五附属医院)医学实验中心,南宁 530022
3.广西中医药大学附属国际壮医医院肿瘤科,南宁 530201
4.南宁市第一人民医院(广西医科大学第五附属医院)血液内科,南宁 530022
Received:16 March 2026,
Revised:2026-06-24,
Accepted:25 June 2026,
Published:15 July 2026
移动端阅览
王彬睿,常峥,覃梅静,等.中药活性成分调控γδ T细胞抗肿瘤免疫功能的研究进展[J].中国药房,2026,37(13):1773-1777.
WANG Binrui,CHANG Zheng,QIN Meijing,et al.Research progress on regulation of antitumor immune function of γδ T cells by active ingredients of traditional Chinese medicine[J].ZHONGGUO YAOFANG,2026,37(13):1773-1777.
王彬睿,常峥,覃梅静,等.中药活性成分调控γδ T细胞抗肿瘤免疫功能的研究进展[J].中国药房,2026,37(13):1773-1777. DOI: 10.6039/j.issn.1001-0408.2026.13.20.
WANG Binrui,CHANG Zheng,QIN Meijing,et al.Research progress on regulation of antitumor immune function of γδ T cells by active ingredients of traditional Chinese medicine[J].ZHONGGUO YAOFANG,2026,37(13):1773-1777. DOI: 10.6039/j.issn.1001-0408.2026.13.20.
γδ T细胞兼具先天性与适应性免疫特征,其抗原识别不依赖经典的主要组织相容性复合体呈递,可直接识别肿瘤代谢异常,在免疫低浸润肿瘤中具有独特应用潜力。本文系统梳理γδ T细胞的生物学特性及其抗肿瘤免疫功能特点,重点综述中药活性成分调控γδ T细胞抗肿瘤免疫功能的相关机制,发现甘草多糖、黄芪多糖可通过促进多种细胞因子表达、调节肠道菌群、改善免疫抑制状态等,增强γδ T细胞的抗肿瘤免疫功能;槲皮素和葛根素可通过调节γδ T细胞的增殖、细胞毒效应分子表达及相关信号通路活性,增强γδ T细胞介导的肿瘤细胞杀伤作用;川楝素可通过下调肿瘤细胞中抗凋亡蛋白表达,增强γδ T细胞对肿瘤细胞的杀伤作用;青蒿琥酯可通过增强γδ T细胞效应功能并减弱肿瘤细胞免疫逃逸能力,促进γδ T细胞介导的抗肿瘤免疫效应。未来可重点探索中药活性成分与γδ T细胞免疫治疗联合应用的协同效应及相关分子机制,明确γδ T细胞发挥抗肿瘤免疫功能的关键靶点。
γδ T cells possess both innate and adaptive immune characteristics. Their antigen recognition is independent of major histocompatibility complex presentation, and they can directly recognize abnormal tumor metabolism, showing unique application potential in tumors with low immune infiltration. This paper systematically sorts out the biological characteristics and antitumor immune functions of γδ T cells, and mainly reviews the relevant mechanisms by which active ingredients of traditional
Chinese medicine regulate γδ T cells to exert antitumor immune functions.
Glycyrrhiza
polysaccharide and
Astragalus
polysaccharide can enhance the antitumor immune function of γδ T cells by promoting the expression of various cytokines, regulating intestinal flora and alleviating immunosuppressive state. Quercetin and puerarin can strengthen γδ T cell-mediated tumor cell killing by regulating the proliferation of γδ T cells, the expression of cytotoxic effector molecules and related signaling pathways. Toosendanin can potentiate γδ T cell-induced tumor cell killing by down-regulating the expression of anti-apoptotic protein in tumor cells. Artesunate can boost γδ T cell-mediated antitumor immune responses by enhancing the effector function of γδ T cells and weakening tumor immune escape. Future research shall focus on exploring the synergistic effects and molecular mechanisms of the combined application of active ingredients of traditional Chinese medicine and γδ T cell immunotherapy, and identifying the key targets for γδ T cells to exert antitumor immune functions.
Sade-Feldman M , Jiao Y J , Chen J H , et al . Resistance to checkpoint blockade therapy through inactivation of antigen presentation [J ] . Nat Commun , 2017 , 8 ( 1 ): 1136 .
Kieffer Y , Hocine H R , Gentric G , et al . Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer [J ] . Cancer Discov , 2020 , 10 ( 9 ): 1330 - 1351 .
Robert C , Long G V , Brady B , et al . Five-year outcomes with nivolumab in patients with wild-type BRAF advanced melanoma [J ] . J Clin Oncol , 2020 , 38 ( 33 ): 3937 - 3946 .
Rohaan M W , Borch T H , van den Berg J H , et al . Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma [J ] . N Engl J Med , 2022 , 387 ( 23 ): 2113 - 2125 .
Locke F L , Miklos D B , Jacobson C A , et al . Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma [J ] . N Engl J Med , 2022 , 386 ( 7 ): 640 - 654 .
Gettinger S , Choi J , Hastings K , et al . Impaired HLA class Ⅰ antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung cancer [J ] . Cancer Discov , 2017 , 7 ( 12 ): 1420 - 1435 .
Michael H , Lenihan A T , Vallas M M , et al . The cytotoxic potential of humanized γδ T cells against human cancer cell lines in vitro [J ] . Cells , 2025 , 14 ( 15 ): 1197 .
闻淑娟 , 张珍连 , 李姗 , 等 . γδ T细胞对弥漫性大B细胞淋巴瘤细胞的杀伤作用及其机制研究 [J/OL ] . 中国医学前沿杂志 (电子版), 2019 , 11 ( 10 ): 103 - 109 . https://www.cnki.com.cn/Article/CJFDTotal-YXQY201910027 https://www.cnki.com.cn/Article/CJFDTotal-YXQY201910027 .
张慧珠 , 杨林 , 刘淑梅 , 等 . 中药活性成分体外逆转肿瘤细胞多药耐药性的研究 [J ] . 中药材 , 2001 , 24 ( 9 ): 655 - 657 .
Duya P A , Chen Y X , Bai L D , et al . Nature products of traditional Chinese medicine provide new ideas in γδ T cell for tumor immunotherapy [J ] . Acupunct Herb Med , 2022 , 2 ( 2 ): 78 - 83 .
Caccamo N , Todaro M , Sireci G , et al . Mechanisms underlying lineage commitment and plasticity of human γδ T cells [J ] . Cell Mol Immunol , 2013 , 10 ( 1 ): 30 - 34 .
Willcox C R , Salim M , Begley C R , et al . Phosphoantigen sensing combines TCR-dependent recognition of the BTN3A IgV domain and germline interaction with BTN2A1 [J ] . Cell Rep , 2023 , 42 ( 4 ): 112321 .
Herrmann T , Karunakaran M M . Phosphoantigen recognition by Vγ9Vδ2 T cells [J ] . Eur J Immunol , 2024 , 54 ( 11 ): 2451068 .
Gray J I , Caron D P , Wells S B , et al . Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span [J ] . Sci Immunol , 2024 , 9 ( 96 ): eadn3954 .
Bauer S , Groh V , Wu J , et al . Activation of NK cells and T cells by NKG2D,a receptor for stress-inducible MICA [J ] . Science , 1999 , 285 ( 5428 ): 727 - 729 .
Poggi A , Venturino C , Catellani S , et al . Vdelta1 T lymphocytes from B-CLL patients recognize ULBP3 expressed on leukemic B cells and up-regulated by trans-retinoic acid [J ] . Cancer Res , 2004 , 64 ( 24 ): 9172 - 9179 .
Xu B , Pizarro J C , Holmes M A , et al . Crystal structure of a gammadelta T-cell receptor specific for the human MHC class Ⅰ homolog MICA [J ] . Proc Natl Acad Sci U S A , 2011 , 108 ( 6 ): 2414 - 2419 .
Castro C D , Boughter C T , Broughton A E , et al . Diversity in recognition and function of human γδ T cells [J ] . Immunol Rev , 2020 , 298 ( 1 ): 134 - 152 .
Wu P , Wu D , Ni C , et al . γδ T17 cells promote the accumulation and expansion of myeloid-derived suppressor cells in human colorectal cancer [J ] . Immunity , 2014 , 40 ( 5 ): 785 - 800 .
Coffelt S B , Kersten K , Doornebal C W , et al . IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis [J ] . Nature , 2015 , 522 ( 7556 ): 345 - 348 .
梅建东 , 刘伦旭 . 白介素-17在肺癌发生及进展中的作用与机制研究进展 [J ] . 中国肺癌杂志 , 2016 , 19 ( 1 ): 46 - 51 .
Kolahchi Z , Rezaei N . Role of T helper 17 in cancer pathology:a double-edge sword [M ] // Cancer Immunology:the Immune System and Tumor . Berlin : Springer , 2025 : 173 - 196 .
Peng G Y , Wang H Y , Peng W Y , et al . Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway [J ] . Immunity , 2007 , 27 ( 2 ): 334 - 348 .
Nixon B G , Gao S Y , Wang X X , et al . TGF-β control of immune responses in cancer:a holistic immuno-oncology perspective [J ] . Nat Rev Immunol , 2023 , 23 ( 6 ): 346 - 362 .
Gao Z F , Bai Y F , Lin A Q , et al . Gamma delta T-cell-based immune checkpoint therapy:attractive candidate for antitumor treatment [J ] . Mol Cancer , 2023 , 22 ( 1 ): 31 .
Meraviglia S , Eberl M , Vermijlen D , et al . In vivo manipulation of Vgamma9Vdelta2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients [J ] . Clin Exp Immunol , 2010 , 161 ( 2 ): 290 - 297 .
Gober H J , Kistowska M , Angman L , et al . Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells [J ] . J Exp Med , 2003 , 197 ( 2 ): 163 - 168 .
Kobayashi H , Tanaka Y , Yagi J , et al . Phase Ⅰ/Ⅱ study of adoptive transfer of γδ T cells in combination with zoledronic acid and IL-2 to patients with advanced renal cell carcinoma [J ] . Cancer Immunol Immunother , 2011 , 60 ( 8 ): 1075 - 1084 .
Lang J M , Kaikobad M R , Wallace M , et al . Pilot trial of interleukin-2 and zoledronic acid to augment γδ T cells as treatment for patients with refractory renal cell carcinoma [J ] . Cancer Immunol Immunother , 2011 , 60 ( 10 ): 1447 - 1460 .
Dieli F , Vermijlen D , Fulfaro F , et al . Targeting human γδ T cells with zoledronate and interleukin-2 for immunotherapy of hormone-refractory prostate cancer [J ] . Cancer Res , 2007 , 67 ( 15 ): 7450 - 7457 .
Nakajima J , Murakawa T , Fukami T , et al . A phase Ⅰ study of adoptive immunotherapy for recurrent non-small-cell lung cancer patients with autologous gammadelta T cells [J ] . Eur J Cardiothorac Surg , 2010 , 37 ( 5 ): 1191 - 1197 .
Capsomidis A , Benthall G , van Acker H H , et al . Chimeric antigen receptor-engineered human gamma delta T cells:enhanced cytotoxicity with retention of cross presentation [J ] . Mol Ther , 2018 , 26 ( 2 ): 354 - 365 .
Bridge J , Mj J , Kim J , et al . Efficient multiplex non-viral engineering and expansion of polyclonal gammadelta CAR-T cells for immunotherapy [J ] . Mol Ther , 2026 , 34 ( 6 ): 3456 - 3471 .
Themeli M , Kloss C C , Ciriello G , et al . Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy [J ] . Nat Biotechnol , 2013 , 31 ( 10 ): 928 - 933 .
Deniger D C , Switzer K , Mi T J , et al . Bispecific T-cells expressing polyclonal repertoire of endogenous γδ T-cell receptors and introduced CD19-specific chimeric antigen receptor [J ] . Mol Ther , 2013 , 21 ( 3 ): 638 - 647 .
Sebestyen Z , Prinz I , DÉchanet-Merville J , et al . Transla- ting gammadelta (γδ) T cells and their receptors into cancer cell therapies [J ] . Nat Rev Drug Discov , 2020 , 19 ( 3 ): 169 - 184 .
Hedges J F , Jutila M A . Harnessing γδ T cells as natural immune modulators [M ] // Mucosal Vaccines . Amsterdam : Elsevier , 2020 : 773 - 787 .
Chen Y X , Li Z D , Bai L D , et al . Glycyrrhiza polysaccharides may have an antitumor effect in γδ T cells through gut microbiota and TLRs/NF-κB pathway in mice [J ] . FEBS Open Bio , 2024 , 14 ( 6 ): 1011 - 1027 .
Ayeka P A , Bian Y H , Githaiga P M , et al . The immunomodulatory activities of licorice polysaccharides ( Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice [J ] . BMC Complement Altern Med , 2017 , 17 ( 1 ): 536 .
Yao X P , Zhang K Q , Zhang X K , et al . Glycyrrhiza polysaccharide-adjuvanted liposomal vaccine potentiates tumor immunotherapy through lymph node-targeted modulation of the DC-T cell axis [J ] . J Exp Clin Cancer Res , 2025 , 45 ( 1 ): 4 .
Sun S Y , Zheng K , Zhao H Y , et al . Regulatory effect of Astragalus polysaccharides on intestinal intraepithelial γδ T cells of tumor bearing mice [J ] . Molecules , 2014 , 19 ( 9 ): 15224 - 15236 .
Lu H Y , Peng T S , Hu X D , et al . Quercetin potentiates the effect of γδ T cells via modulating the expressions of granzyme B,perforin and IFN-γ and also regulates the Wnt/β-catenin signaling pathway in human colon cancer cells [J ] . Bangladesh J Pharmacol , 2015 , 10 ( 2 ): 251 .
袁涛 , 朱炳喜 , 刘军权 , 等 . 葛根素对γδ T细胞杀伤肝癌SMMC-7721细胞的影响 [J ] . 中国现代应用药学 , 2015 , 32 ( 4 ): 419 - 424 .
郁峰 , 徐统球 , 陈诚豪 , 等 . 川楝素与γδ T细胞协同抗结直肠癌的作用及机制研究 [J ] . 中国病理生理杂志 , 2017 , 33 ( 11 ): 2020 - 2025 .
Qian P , Zhang Y W , Zhou Z H , et al . Artesunate enhances γδ T-cell-mediated antitumor activity through augmenting γδ T-cell function and reversing immune escape of HepG2 cells [J ] . Immunopharmacol Immunotoxicol , 2018 , 40 ( 2 ): 107 - 116 .
0
Views
0
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621
