肿瘤微环境靶向治疗策略的研究进展
Research Progress of Targeted Therapy Strategies in Tumor Microenvironment
摘要: 随着肿瘤与肿瘤微环境(TME)相关研究越来越透彻，基于TME的靶向疗法也开始备受关注，并且与常规疗法的联合治疗也呈现出一定的疗效。因此，本文主要针对TME中的脉管系统、特异性细胞外基质、成纤维细胞、免疫细胞以及趋化因子的靶向疗法进行了阐述。研究表明，肿瘤微环境是一个复杂的生态系统，除癌细胞外，还依赖于TME中存在的支持成分，这些支持成分对肿瘤的生长、转移和耐药性都有重要影响。因此，针对TME中各个支持成分的靶向治疗将在抑制肿瘤生长，侵袭转移，以及耐药性上具有重要的意义。
Abstract: With the research on tumor and tumor microenvironment (TME) becoming more and more thorough, targeted therapy based on TME has begun to attract attention, and the combination therapy with conventional therapy has also shown certain efficacy. Therefore, this article focuses on the targeted therapy of vascular system, specific extracellular matrix, fibroblasts, immune cells and chemokines in TME. Studies have shown that the tumor microenvironment is a complex ecosystem that depends on supporting components present in the TME in addition to cancer cells, which have important effects on tumor growth, metastasis, and drug resistance. Therefore, targeted therapy targeting each supporting component of TME will be of great significance in inhibiting tumor growth, invasion, metastasis, and drug resistance.
文章引用：彭朝胜, 杨泽旭. 肿瘤微环境靶向治疗策略的研究进展[J]. 临床医学进展, 2026, 16(1): 1083-1090. https://doi.org/10.12677/acm.2026.161141

参考文献

[1] Testa, U., Pelosi, E. and Castelli, G. (2020) Endothelial Progenitors in the Tumor Microenvironment. In: Birbrair, A., Ed., Tumor Microenvironment, Springer International Publishing, 85-115. [Google Scholar] [CrossRef] [PubMed]
[2] Dumitru, C.S. and Raica, M. (2024) A Splice Form of VEGF, a Potential Anti-Angiogenetic Form of Head and Neck Squamous Cell Cancer Inhibition. International Journal of Molecular Sciences, 25, Article No. 8855. [Google Scholar] [CrossRef] [PubMed]
[3] Incio, J., Ligibel, J.A., McManus, D.T., Suboj, P., Jung, K., Kawaguchi, K., et al. (2018) Obesity Promotes Resistance to Anti-VEGF Therapy in Breast Cancer by Up-Regulating IL-6 and Potentially FGF-2. Science Translational Medicine, 10, eaag0945. [Google Scholar] [CrossRef] [PubMed]
[4] Horn, L.A., Chariou, P.L., Gameiro, S.R., Qin, H., Iida, M., Fousek, K., et al. (2022) Remodeling the Tumor Microenvironment via Blockade of LAIR-1 and TGF-β Signaling Enables PD-L1-Mediated Tumor Eradication. Journal of Clinical Investigation, 132, e155148. [Google Scholar] [CrossRef] [PubMed]
[5] Tucker, R.P. and Degen, M. (2022) Revisiting the Tenascins: Exploitable as Cancer Targets? Frontiers in Oncology, 12, Article ID: 908247. [Google Scholar] [CrossRef] [PubMed]
[6] Sapudom, J., Riedl, P., Schricker, M., Kroy, K. and Pompe, T. (2024) Physical Network Regimes of 3D Fibrillar Collagen Networks Trigger Invasive Phenotypes of Breast Cancer Cells. Biomaterials Advances, 163, Article ID: 213961. [Google Scholar] [CrossRef] [PubMed]
[7] Jiang, Z., Fu, Y. and Shen, H. (2024) Development of Intratumoral Drug Delivery Based Strategies for Antitumor Therapy. Drug Design, Development and Therapy, 18, 2189-2202. [Google Scholar] [CrossRef] [PubMed]
[8] Weiss, T., Puca, E., Silginer, M., Hemmerle, T., Pazahr, S., Bink, A., et al. (2020) Immunocytokines Are a Promising Immunotherapeutic Approach against Glioblastoma. Science Translational Medicine, 12, eabb2311. [Google Scholar] [CrossRef] [PubMed]
[9] He, S., Hao, L., Chen, Y., Gong, B. and Xu, X. (2025) Chinese Herbal Jianpi Jiedu Formula Suppressed Colorectal Cancer Growth in Vitro and in Vivo via Modulating Hypoxia-Inducible Factor 1 Alpha-Mediated Fibroblasts Activation. Journal of Ethnopharmacology, 337, Article ID: 118753. [Google Scholar] [CrossRef] [PubMed]
[10] Zhao, L., Pang, Y., Zhou, Y., Chen, J., Fu, H., Guo, W., et al. (2024) Antitumor Efficacy and Potential Mechanism of Fap-Targeted Radioligand Therapy Combined with Immune Checkpoint Blockade. Signal Transduction and Targeted Therapy, 9, Article No. 142. [Google Scholar] [CrossRef] [PubMed]
[11] Geng, F., Dong, L., Bao, X., Guo, Q., Guo, J., Zhou, Y., et al. (2022) Cafs/Tumor Cells Co-Targeting DNA Vaccine in Combination with Low-Dose Gemcitabine for the Treatment of Panc02 Murine Pancreatic Cancer. Molecular Therapy—Oncolytics, 26, 304-313. [Google Scholar] [CrossRef] [PubMed]
[12] Pecoraro, C., Carbone, D., Sciano, F., et al. (2024) Exploring the Therapeutic Potential of a Novel Series of Imidazothiadiazoles Targeting Focal Adhesion Kinase (FAK) for Pancreatic Cancer Treatment: Synthesis, Mechanistic Insights and Promising Antitumor and Safety Profile. Journal of Drug Targeting, 32, 1278-1294.
[13] Peng, H., Yang, M., Feng, K., Lv, Q. and Zhang, Y. (2024) Semaphorin 3C (Sema3C) Reshapes Stromal Microenvironment to Promote Hepatocellular Carcinoma Progression. Signal Transduction and Targeted Therapy, 9, Article No. 169. [Google Scholar] [CrossRef] [PubMed]
[14] Fujiwara, T., Yakoub, M.A., Chandler, A., Christ, A.B., Yang, G., Ouerfelli, O., et al. (2021) CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-Cell Infiltration in the Sarcoma Microenvironment. Molecular Cancer Therapeutics, 20, 1388-1399. [Google Scholar] [CrossRef] [PubMed]
[15] Yang, Z., Li, H., Wang, W., Zhang, J., Jia, S., Wang, J., et al. (2019) CCL2/CCR2 Axis Promotes the Progression of Salivary Adenoid Cystic Carcinoma via Recruiting and Reprogramming the Tumor-Associated Macrophages. Frontiers in Oncology, 9, Article No. 231. [Google Scholar] [CrossRef] [PubMed]
[16] Modak, R.V., de Oliveira Rebola, K.G., McClatchy, J., Mohammadhosseini, M., Damnernsawad, A., Kurtz, S.E., et al. (2024) Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia. Clinical Cancer Research, 30, 2245-2259. [Google Scholar] [CrossRef] [PubMed]
[17] Chang, R., Gulley, J.L. and Fong, L. (2023) Vaccinating against Cancer: Getting to Prime Time. Journal for ImmunoTherapy of Cancer, 11, e006628. [Google Scholar] [CrossRef] [PubMed]
[18] Si, F., Liu, X., Tao, Y., Zhang, Y., Ma, F., Hsueh, E.C., et al. (2024) Blocking Senescence and Tolerogenic Function of Dendritic Cells Induced by γδ Treg Cells Enhances Tumor-Specific Immunity for Cancer Immunotherapy. Journal for ImmunoTherapy of Cancer, 12, e008219. [Google Scholar] [CrossRef] [PubMed]
[19] Jacobson, C.A., Chavez, J.C., Sehgal, A.R., William, B.M., Munoz, J., Salles, G., et al. (2022) Axicabtagene Ciloleucel in Relapsed or Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5): A Single-Arm, Multicentre, Phase 2 Trial. The Lancet Oncology, 23, 91-103. [Google Scholar] [CrossRef] [PubMed]
[20] Nishimoto, K.P., Barca, T., Azameera, A., Makkouk, A., Romero, J.M., Bai, L., et al. (2022) Allogeneic CD20‐Targeted γδ T Cells Exhibit Innate and Adaptive Antitumor Activities in Preclinical B‐Cell Lymphoma Models. Clinical & Translational Immunology, 11, e1373. [Google Scholar] [CrossRef] [PubMed]
[21] Pan, J., Niu, Q., Deng, B., Liu, S., Wu, T., Gao, Z., et al. (2019) CD22 CAR T-Cell Therapy in Refractory or Relapsed B Acute Lymphoblastic Leukemia. Leukemia, 33, 2854-2866. [Google Scholar] [CrossRef] [PubMed]
[22] Brandenburg, A., Heine, A. and Brossart, P. (2024) Next-Generation Cancer Vaccines and Emerging Immunotherapy Combinations. Trends in Cancer, 10, 749-769. [Google Scholar] [CrossRef] [PubMed]
[23] Hurton, L.V., Singh, H., Najjar, A.M., Switzer, K.C., Mi, T., Maiti, S., et al. (2016) Tethered IL-15 Augments Antitumor Activity and Promotes a Stem-Cell Memory Subset in Tumor-Specific T Cells. Proceedings of the National Academy of Sciences, 113, E7788-E97. [Google Scholar] [CrossRef] [PubMed]
[24] Leidner, R., Sanjuan Silva, N., Huang, H., Sprott, D., Zheng, C., Shih, Y., et al. (2022) Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer. New England Journal of Medicine, 386, 2112-2119. [Google Scholar] [CrossRef] [PubMed]
[25] Zengarini, C., Guglielmo, A., Mussi, M., Motta, G., Agostinelli, C., Sabattini, E., et al. (2024) A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments. Antibodies, 13, Article No. 32. [Google Scholar] [CrossRef] [PubMed]
[26] Nagira, Y., Nagira, M., Nagai, R., Nogami, W., Hirata, M., Ueyama, A., et al. (2023) S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells. Molecular Cancer Therapeutics, 22, 1063-1072. [Google Scholar] [CrossRef] [PubMed]
[27] Zhao, L., Wang, G., Qi, H., Yu, L., Yin, H., Sun, R., et al. (2024) LINC00330/CCL2 Axis-Mediated ESCC TAM Reprogramming Affects Tumor Progression. Cellular & Molecular Biology Letters, 29, Article No. 77. [Google Scholar] [CrossRef] [PubMed]
[28] Noel, M., O’Reilly, E.M., Wolpin, B.M., Ryan, D.P., Bullock, A.J., Britten, C.D., et al. (2019) Phase 1b Study of a Small Molecule Antagonist of Human Chemokine (C-C Motif) Receptor 2 (PF-04136309) in Combination with Nab-Paclitaxel/Gemcitabine in First-Line Treatment of Metastatic Pancreatic Ductal Adenocarcinoma. Investigational New Drugs, 38, 800-811. [Google Scholar] [CrossRef] [PubMed]
[29] Yin, H., Zhou, X., Huang, Y., King, G.J., Collins, B.M., Gao, Y., et al. (2021) Rational Design of Potent Peptide Inhibitors of the PD-1:PD-L1 Interaction for Cancer Immunotherapy. Journal of the American Chemical Society, 143, 18536-18547. [Google Scholar] [CrossRef] [PubMed]
[30] Gurung, S., Khan, F., Gunassekaran, G.R., Yoo, J.D., Poongkavithai Vadevoo, S.M., Permpoon, U., et al. (2020) Phage Display-Identified Pd-L1-Binding Peptides Reinvigorate T-Cell Activity and Inhibit Tumor Progression. Biomaterials, 247, Article ID: 119984. [Google Scholar] [CrossRef] [PubMed]
[31] Akinleye, A. and Rasool, Z. (2019) Immune Checkpoint Inhibitors of PD-L1 as Cancer Therapeutics. Journal of Hematology & Oncology, 12, Article No. 92. [Google Scholar] [CrossRef] [PubMed]
[32] Colombo, N., Biagioli, E., Harano, K., Galli, F., Hudson, E., Antill, Y., et al. (2024) Atezolizumab and Chemotherapy for Advanced or Recurrent Endometrial Cancer (Attend): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 25, 1135-1146. [Google Scholar] [CrossRef] [PubMed]
[33] West, H., McCleod, M., Hussein, M., Morabito, A., Rittmeyer, A., Conter, H.J., et al. (2019) Atezolizumab in Combination with Carboplatin Plus Nab-Paclitaxel Chemotherapy Compared with Chemotherapy Alone as First-Line Treatment for Metastatic Non-Squamous Non-Small-Cell Lung Cancer (IMpower130): A Multicentre, Randomised, Open-Label, Phase 3 Trial. The Lancet Oncology, 20, 924-937. [Google Scholar] [CrossRef] [PubMed]
[34] Schmid, P., Rugo, H.S., Adams, S., Schneeweiss, A., Barrios, C.H., Iwata, H., et al. (2020) Atezolizumab plus Nab-Paclitaxel as First-Line Treatment for Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer (IMpassion130): Updated Efficacy Results from a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. The Lancet Oncology, 21, 44-59. [Google Scholar] [CrossRef] [PubMed]
[35] Galsky, M.D., Arija, J.Á.A., Bamias, A., Davis, I.D., De Santis, M., Kikuchi, E., et al. (2020) Atezolizumab with or without Chemotherapy in Metastatic Urothelial Cancer (IMvigor130): A Multicentre, Randomised, Placebo-Controlled Phase 3 Trial. The Lancet, 395, 1547-1557. [Google Scholar] [CrossRef] [PubMed]
[36] Brave, M.H., Maguire, W.F., Weinstock, C., et al. (2024) FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma. Clinical Cancer Research, 30, 4815-4821.
[37] Hodi, F.S., O’Day, S.J., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., et al. (2010) Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. New England Journal of Medicine, 363, 711-723. [Google Scholar] [CrossRef] [PubMed]
[38] Wong, J.S.L., Kwok, G.G.W., Tang, V., Li, B.C.W., Leung, R., Chiu, J., et al. (2021) Ipilimumab and Nivolumab/Pembrolizumab in Advanced Hepatocellular Carcinoma Refractory to Prior Immune Checkpoint Inhibitors. Journal for ImmunoTherapy of Cancer, 9, e001945. [Google Scholar] [CrossRef] [PubMed]

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