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Feifei Li, Youyang Shi, Mei Ma, Xiaojuan Yang, Xiaosong Chen, Ying Xie, Sheng Liu. Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100977
Citation: Feifei Li, Youyang Shi, Mei Ma, Xiaojuan Yang, Xiaosong Chen, Ying Xie, Sheng Liu. Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.100977

Xianling Lianxia formula improves the efficacy of trastuzumab by enhancing NK cell-mediated ADCC in HER2-positive BC

doi: 10.1016/j.jpha.2024.100977
  • Received Date: Oct. 12, 2023
  • Accepted Date: Apr. 08, 2024
  • Rev Recd Date: Feb. 08, 2024
  • Available Online: Apr. 13, 2024
  • Trastuzumab has improved survival rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), but drug resistance leads to treatment failure. Natural killer (NK) cell-mediated antibody-dependent cell cytotoxicity (ADCC) represents an essential antitumor immune mechanism of trastuzumab. Traditional Chinese medicine (TCM) has been used for centuries to treat diseases because of its capacity to improve immune responses. Xianling Lianxia formula (XLLXF), based on the principle of “strengthening body and eliminating toxin”, exhibits a synergistic effect in the trastuzumab treatment of patients with HER2-positive BC. Notably, this synergistic effect of XLLXF was executed by enhancing NK cells and ADCC, as demonstrated through in vitro co-culture of NK cells and BC cells and in vivo intervention experiments. Mechanistically, the augmented impact of XLLXF on NK cells is linked to a decrease in cytokine inducible SH2 containing protein (CISH) expression, which in turn activates the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 5 (STAT5) pathway. Collectively, these findings suggested that XLLXF holds promise for enhancing NK cell function and sensitizing patients with HER2-positive BC to trastuzumab.
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  • [1]
    R.L. Siegel, K.D. Miller, N.S. Wagle, et al., Cancer statistics, 2023, CA Cancer J. Clin. 73(2023) 17-48.
    [2]
    S. Loibl, L. Gianni, HER2-positive breast cancer, Lancet 389(2017) 2415-2429.
    [3]
    D.J. Slamon, B. Leyland-Jones, S. Shak, et al., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2, N. Engl. J. Med. 344(2001) 783-792.
    [4]
    C.S. Wynn, S.C. Tang, Anti-HER2 therapy in metastatic breast cancer: Many choices and future directions, Cancer Metastasis Rev. 41(2022) 193-209.
    [5]
    K.S. Vega Cano, D.H. Marmolejo Castañeda, S. Escrivá-de-Romaní, et al., Systemic therapy for HER2-positive metastatic breast cancer: Current and future trends, Cancers 15(2022), 51.
    [6]
    H. Kennecke, R. Yerushalmi, R. Woods, et al., Metastatic behavior of breast cancer subtypes, J. Clin. Oncol. 28(2010) 3271-3277.
    [7]
    N. Harbeck, C.S. Huang, S. Hurvitz, et al., Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): An open-label, randomised, phase 3 trial, Lancet Oncol. 17(2016) 357-366.
    [8]
    G. Nader-Marta, D. Martins-Branco, E. de Azambuja, How we treat patients with metastatic HER2-positive breast cancer, ESMO Open 7(2022), 100343.
    [9]
    F. Li, S. Liu, Focusing on NK cells and ADCC: A promising immunotherapy approach in targeted therapy for HER2-positive breast cancer, Front. Immunol. 13(2022), 1083462.
    [10]
    F.A.I. Ehlers, N.A. Beelen, M. van Gelder, et al., ADCC-inducing antibody trastuzumab and selection of KIR-HLA ligand mismatched donors enhance the NK cell anti-breast cancer response, Cancers 13(2021), 3232.
    [11]
    R. Du, X. Zhang, X. Lu, et al., PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity, Drug Resist. Updat. Rev. Comment. Antimicrob. Anticancer Chemother. 68(2023), 100947.
    [12]
    G.D. Rak, E.M. Mace, P.P. Banerjee, et al., Natural killer cell lytic granule secretion occurs through a pervasive actin network at the immune synapse, PLoS Biol. 9(2011), e1001151.
    [13]
    X. Ren, M. Peng, P. Xing, et al., Blockade of the immunosuppressive KIR2DL5/PVR pathway elicits potent human NK cell-mediated antitumor immunity, J. Clin. Investig. 132(2022), e163620.
    [14]
    B. Lipinski, P. Arras, L. Pekar, et al., NKp46-specific single domain antibodies enable facile engineering of various potent NK cell engager formats, Protein Sci. a Publ. Protein Soc. 32(2023), e4593.
    [15]
    A. Glasner, H. Ghadially, C. Gur, et al., Recognition and prevention of tumor metastasis by the NK receptor NKp46/NCR1, J. Immunol. Baltim. Md 1950188(2012) 2509-2515.
    [16]
    L. Gauthier, A. Morel, N. Anceriz, et al., Multifunctional natural killer cell engagers targeting NKp46 trigger protective tumor immunity, Cell 177(2019) 1701-1713.e16.
    [17]
    P. Peng, Y. Lou, S. Wang, et al., Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy, J. Immunother. Cancer 10(2022), e005769.
    [18]
    S. Vasu, S. He, C. Cheney, et al. Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts, Blood 127(2016) 2879-2889.
    [19]
    J. Xing, S. Liu, X. Tang, et al., Retrospective analysis of postoperative formula with additions and subtractions for the treatment of HER-2 overexpression breast cancer, Liaoning University of Traditional Chinese Medicine 24(2022) 112-120.
    [20]
    G. Chen, Z. Cao, Z. Shi, et al., Microbiome analysis combined with targeted metabolomics reveal immunological anti-tumor activity of icariside I in a melanoma mouse model, Biomedecine Pharmacother. 140(2021), 111542.
    [21]
    L. Song, X. Chen, L. Mi, et al., Icariin-induced inhibition of SIRT6/NF-κB triggers redox mediated apoptosis and enhances anti-tumor immunity in triple-negative breast cancer, Cancer Sci 111(2020) 4242-4256.
    [22]
    S. Dandawate, L. Williams, N. Joshee, et al., Scutellaria extract and wogonin inhibit tumor-mediated induction of T(reg) cells via inhibition of TGF-β1 activity, Cancer Immunol. Immunother. 61(2012) 701-711.
    [23]
    W. Li, Q. Xu, Y. He, et al., Anti-tumor effect of Steamed Codonopsis lanceolata in H22 tumor-bearing mice and its possible mechanism, Nutrients 7(2015) 8294-8307.
    [24]
    F. Li, Y. Shi, Y. Zhang, et al., Investigating the mechanism of Xian-ling-Lian-Xia-Fang for inhibiting vasculogenic mimicry in triple negative breast cancer via blocking VEGF/MMPs pathway, Chin. Med. 17(2022), 44.
    [25]
    J. Wu, F. Gao, C. Wang, et al., IL-6 and IL-8 secreted by tumour cells impair the function of NK cells via the STAT3 pathway in oesophageal squamous cell carcinoma, J. Exp. Clin. Cancer Res. 38(2019), 321.
    [26]
    L. Li, T. Liu, L. Shi, et al., HER2-targeted dual radiotracer approach with clinical potential for noninvasive imaging of trastuzumab-resistance caused by epitope masking, Theranostics 12(2022) 5551-5563.
    [27]
    J. Scerri, C. Scerri, F. Schäfer-Ruoff, et al., PKC-mediated phosphorylation and activation of the MEK/ERK pathway as a mechanism of acquired trastuzumab resistance in HER2-positive breast cancer, Front. Endocrinol. 13(2022), 1010092.
    [28]
    W. Li, J. Zhou, X. Wang, et al., CD49a+CD49b+ NK cells induced by viral infection reflect an activated state of conventional NK cells, Sci. China Life Sci. 63(2020) 1725-1733.
    [29]
    L. Martinet, M.J. Smyth, Balancing natural killer cell activation through paired receptors, Nat. Rev. Immunol. 15(2015) 243-254.
    [30]
    M.D. Miljkovic, S.P. Dubois, J.R. Müller, et al., Interleukin-15 augments NK cell-mediated ADCC of alemtuzumab in patients with CD52+ T-cell malignancies, Blood Adv. 7(2023) 384-394.
    [31]
    F. Carrette, E. Vivier, NKG2A blocks the anti-metastatic functions of natural killer cells, Cancer Cell 41(2023) 232-234.
    [32]
    G. Zheng, Z. Guo, W. Li, et al., Interaction between HLA-G and NK cell receptor KIR2DL4 orchestrates HER2-positive breast cancer resistance to trastuzumab, Signal Transduct. Target. Ther. 6(2021), 236.
    [33]
    J. Yang, A. Kumar, A.E. Vilgelm, et al., Loss of CXCR4 in myeloid cells enhances antitumor immunity and reduces melanoma growth through NK cell and FASL mechanisms, Cancer Immunol. Res. 6(2018) 1186-1198.
    [34]
    K. Fousek, L.A. Horn, H. Qin, et al., An interleukin-15 superagonist enables antitumor efficacy of natural killer cells against all molecular variants of SCLC, J. Thorac. Oncol. 18(2023) 350-368.
    [35]
    R.B. Delconte, T.B. Kolesnik, L.F. Dagley, et al., CIS is a potent checkpoint in NK cell-mediated tumor immunity, Nat. Immunol. 17(2016) 816-824.
    [36]
    H. Zhu, R.H. Blum, D. Bernareggi, et al., Metabolic reprograming via deletion of CISH in human iPSC-derived NK cells promotes InVivo persistence and enhances anti-tumor activity, Cell Stem Cell 27(2020) 224-237.e6.
    [37]
    D. Cameron, M.J. Piccart-Gebhart, R.D. Gelber, et al., 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: Final analysis of the HERceptin Adjuvant (HERA) trial, Lancet 389(2017) 1195-1205.
    [38]
    R. Ghosh, A. Narasanna, S.E. Wang, et al., Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers, Cancer Res. 71(2011) 1871-1882.
    [39]
    H. Maadi, Z. Wang, A novel mechanism underlying the inhibitory effects of trastuzumab on the growth of HER2-positive breast cancer cells, Cells 11(2022), 4093.
    [40]
    S. Chumsri, Advancing outcomes of metastatic HER2-positive breast cancer, Lancet 401(2023) 1746-1747.
    [41]
    M. Shang, Y. Chi, J. Zhang, et al., The therapeutic effectiveness of neoadjuvant trastuzumab plus chemotherapy for HER2-positive breast cancer can be predicted by tumor-infiltrating lymphocytes and PD-L1 expression, Front. Oncol. 11(2021), 706606.
    [42]
    S. Bruni, F.L. Mauro, C.J. Proietti, et al., Blocking soluble TNFα sensitizes HER2-positive breast cancer to trastuzumab through MUC4 downregulation and subverts immunosuppression, J. Immunother. Cancer 11(2023), e005325.
    [43]
    F. Meng, S. Zhang, J. Xie, et al., Leveraging CD16 fusion receptors to remodel the immune response for enhancing anti-tumor immunotherapy in iPSC-derived NK cells, J. Hematol. Oncol. 16(2023), 62.
    [44]
    L. Mecklenburg, B. Tychsen, R. Paus, Learning from nudity: Lessons from the nude phenotype, Exp. Dermatol. 14(2005) 797-810.
    [45]
    J. Fogh, J.M. Fogh, T. Orfeo, One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice, J. Natl. Cancer Inst. 59(1977) 221-226.
    [46]
    L.D. Shultz, F. Ishikawa, D.L. Greiner, Humanized mice in translational biomedical research, Nat. Rev. Immunol. 7(2007) 118-130.
    [47]
    I. Szadvari, O. Krizanova, P. Babula, Athymic nude mice as an experimental model for cancer treatment, Physiol. Res. 65(2016) S441-S453.
    [48]
    J. Lv, L. Qin, R. Zhao, et al., Disruption of CISH promotes the antitumor activity of human T cells and decreases PD-1 expression levels, Mol. Ther. Oncolytics 28(2022) 46-58.
    [49]
    F. Souza-Fonseca-Guimaraes, G.R. Rossi, L.F. Dagley, et al., TGFβ and CIS inhibition overcomes NK-cell suppression to restore antitumor immunity, Cancer Immunol. Res. 10(2022) 1047-1054.
    [50]
    J. Bi, C. Huang, X. Jin, et al., TIPE2 deletion improves the therapeutic potential of adoptively transferred NK cells, J. Immunother. Cancer 11(2023), e006002.
    [51]
    K.M. Maalej, M. Merhi, V.P. Inchakalody, et al., CAR-cell therapy in the era of solid tumor treatment: Current challenges and emerging therapeutic advances, Mol. Cancer 22(2023), 20.
    [52]
    R. Elahi, A.H. Heidary, K. Hadiloo, et al., Chimeric antigen receptor-engineered natural killer (CAR NK) cells in cancer treatment; recent advances and future prospects, Stem Cell Rev. Rep. 17(2021) 2081-2106.
    [53]
    H. Ebrahimiyan, A. Tamimi, B. Shokoohian, et al., Novel insights in CAR-NK cells beyond CAR-T cell technology; promising advantages, Int. Immunopharmacol. 106(2022), 108587.
    [54]
    O. Cienfuegos-Jimenez, E. Vazquez-Garza, A. Rojas-Martinez, CAR-NK cells for cancer therapy: Molecular redesign of the innate antineoplastic response, Curr. Gene Ther. 22(2022) 303-318.
    [55]
    B. Cao, M. Liu, L. Wang, et al., Use of chimeric antigen receptor NK-92 cells to target mesothelin in ovarian cancer, Biochem. Biophys. Res. Commun. 524(2020) 96-102.
    [56]
    S. Klöß, O. Oberschmidt, M. Morgan, et al., Optimization of human NK cell manufacturing: Fully automated separation, improved ex vivo expansion using IL-21 with autologous feeder cells, and generation of anti-CD123-CAR-expressing effector cells, Hum. Gene Ther. 28(2017) 897-913.
    [57]
    J. Tanaka, J.S. Miller, Recent progress in and challenges in cellular therapy using NK cells for hematological malignancies, Blood Rev. 44(2020), 100678.
    [58]
    I. Pedroza-Pacheco, A. Madrigal, A. Saudemont, Interaction between natural killer cells and regulatory T cells: Perspectives for immunotherapy, Cell. Mol. Immunol. 10(2013) 222-229.
    [59]
    T.A. Waldmann, E. Lugli, M. Roederer, et al., Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL-15 in rhesus macaques, Blood 117(2011) 4787-4795.
    [60]
    T. Bald, M.F. Krummel, M.J. Smyth, et al., The NK cell-cancer cycle: Advances and new challenges in NK cell-based immunotherapies, Nat. Immunol. 21(2020) 835-847.
    [61]
    C. Di Nitto, E. Gilardoni, J. Mock, et al., An engineered IFNγ-antibody fusion protein with improved tumor-homing properties, Pharmaceutics 15(2023), 377.
    [62]
    Y. Miao, X. Fan, L. Wei, et al., Lizhong Decoction ameliorates pulmonary infection secondary to severe traumatic brain injury in rats by regulating the intestinal physical barrier and immune response, J. Ethnopharmacol. 311(2023), 116346.
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