切换至 "中华医学电子期刊资源库"

中华肥胖与代谢病电子杂志 ›› 2025, Vol. 11 ›› Issue (03) : 249 -255. doi: 10.3877/cma.j.issn.2095-9605.2025.03.013

综述

肥胖相关肿瘤免疫治疗研究进展
边孜力, 刘仕锦, 张怡然, 潘运龙()   
  1. 510632 广州,暨南大学附属第一医院胃肠外科
  • 收稿日期:2025-05-06 出版日期:2025-08-30
  • 通信作者: 潘运龙

Advances in immunotherapy for obesity-related tumors

Zili Bian, Shijin Liu, Yiran Zhang, Yunlong Pan()   

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
  • Received:2025-05-06 Published:2025-08-30
  • Corresponding author: Yunlong Pan
引用本文:

边孜力, 刘仕锦, 张怡然, 潘运龙. 肥胖相关肿瘤免疫治疗研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(03): 249-255.

Zili Bian, Shijin Liu, Yiran Zhang, Yunlong Pan. Advances in immunotherapy for obesity-related tumors[J/OL]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(03): 249-255.

肥胖不仅是多种癌症发生、进展及转移的重要危险因素,还可能通过影响肿瘤免疫微环境使肿瘤免疫治疗疗效更显著,从而抑制肿瘤,形成"肥胖悖论"。肥胖可以通过改变瘦素、脂联素的水平,导致异常信号通路的激活、免疫细胞的功能受损,从而促进肿瘤发生,还可能通过影响肿瘤免疫微环境使肿瘤免疫治疗的疗效更显著,抑制肿瘤进展,但具体的机制目前尚不清楚。本文综述了肥胖通过多种机制重塑肿瘤微环境、影响免疫细胞功能及肥胖与免疫治疗疗效关联性的研究进展,旨在为优化肿瘤免疫治疗策略提供理论依据。

Obesity is not only an important risk factor for the occurrence, progression and metastasis of many types of cancer, but also may affect the tumor immune microenvironment to make the efficacy of tumor immunotherapy more significant, thus inhibiting the tumor, forming the "obesity paradox". Obesity can promote tumorigenesis by altering the levels of leptin and lipocalin, leading to the activation of abnormal signaling pathways and impaired immune cell function, and may also inhibit tumor progression by affecting the tumor immune microenvironment to make the efficacy of tumor immunotherapy more significant, but the specific mechanism is still unclear. This paper reviews the research progress of obesity through multiple mechanisms to remodel the tumor microenvironment, influence immune cell function, and the correlation between obesity and immunotherapy efficacy, aiming to provide a theoretical basis for optimizing tumor immunotherapy strategy.

表1 肥胖对肿瘤微环境免疫细胞的影响机制
表2 靶向肥胖的肿瘤免疫治疗策略
[1]
Mallya S, Gangadhar V, Aldrin SE, et al. Insights into the molecular and genetic role of obesity in breast cancer pathogenesis [J]. Cancer biology & therapy, 2025, 26(1): 2501345
[2]
Pati S, Irfan W, Jameel A, et al. Obesity and cancer: A current overview of epidemiology, pathogenesis, outcomes, and management [J]. Cancers, 2023, 15(2): 485.
[3]
Murphy WJ, Longo DL. The surprisingly positive association between obesity and cancer immunotherapy efficacy [J]. JAMA, 2019, 321(13): 1247-1248.
[4]
Bader JE, Wolf MM, Lupica-Tondo GL, et al. Obesity induces PD-1 on macrophages to suppress anti-tumour immunity [J]. Nature, 2024, 630(8018): 968-975.
[5]
De Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth [J]. Cancer cell, 2023, 41(3): 374-403.
[6]
Liu C, Li X. Role of leptin and adiponectin in immune response and inflammation [J]. International immunopharmacology, 2025, 161: 115082.
[7]
Yang J, He J, Feng Y, et al. Obesity contributes to hepatocellular carcinoma development via immunosuppressive microenvironment remodeling [J]. Frontiers in immunology, 2023, 14: 1166440.
[8]
Nepal S, Kim MJ, Hong JT, et al. Autophagy induction by leptin contributes to suppression of apoptosis in cancer cells and xenograft model: involvement of p53/FoxO3A axis [J]. Oncotarget, 2015, 6(9): 7166-7181.
[9]
Ren G, Guo JH, Feng CL, et al. Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model [J]. Molecular therapy oncolytics, 2022, 26: 372-386.
[10]
Li F, Zhao S, Guo T, et al. The nutritional cytokine leptin promotes NSCLC by activating the PI3K/AKT and MAPK/ERK pathways in NSCLC cells in a paracrine manner [J]. BioMed research international, 2019, 2019: 2585743.
[11]
Lin MC, Wang FY, Kuo YH, et al. Cancer chemopreventive effects of lycopene: suppression of MMP-7 expression and cell invasion in human colon cancer cells [J]. Journal of agricultural and food chemistry, 2011, 59(20): 11304-11318.
[12]
Gorska E, Popko K, Stelmaszczyk-Emmel A, et al. Leptin receptors [J]. European journal of medical research, 2010, 15(Suppl 2): 50-54.
[13]
Wang H, Wang HS, Zhou BH, et al. Epithelial-mesenchymal transition (EMT) induced by TNF-α requires AKT/GSK-3β-mediated stabilization of snail in colorectal cancer [J]. PloS one, 2013, 8(2): e56664.
[14]
Nri-Ezedi CA, Ulasi T, Chukwuka J, et al. Serum total adiponectin in healthy pre-pubertal nigerian school children [J]. Nigerian journal of clinical practice, 2021, 24(6): 821-827.
[15]
Sun B, Karin M. Obesity, inflammation, and liver cancer [J]. Journal of hepatology, 2012, 56(3): 704-713.
[16]
Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review [J]. British journal of cancer, 2006, 94(9): 1221-1225.
[17]
Saxena NK, Fu PP, Nagalingam A, et al. Adiponectin modulates C-jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma [J]. Gastroenterology, 2010, 139(5): 1762-1773.
[18]
Parida S, Siddharth S, Sharma D. Adiponectin, obesity, and cancer: clash of the bigwigs in health and disease [J]. International journal of molecular sciences, 2019, 20(10): 2519.
[19]
Lohmann AE, Soldera SV, Pimentel I, et al. Association of obesity with breast cancer outcome in relation to cancer subtypes: a meta-analysis [J]. Journal of the National Cancer Institute, 2021, 113(11): 1465-1475.
[20]
Xu K, Yin N, Peng M, et al. Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity [J]. Science (New York, N.Y.), 2021, 371(6527): 405-410.
[21]
Turbitt WJ, Buchta Rosean C, Weber KS, et al. Obesity and CD8+ T cell metabolism: Implications for anti-tumor immunity and cancer immunotherapy outcomes [J]. Immunological reviews, 2020, 295(1): 203-219.
[22]
Ma S, Ming Y, Wu J, et al. Cellular metabolism regulates the differentiation and function of T-cell subsets [J]. Cellular & molecular immunology, 2024, 21(5): 419-435.
[23]
Cao J, Liao S, Zeng F, et al. Effects of altered glycolysis levels on CD8+ T cell activation and function [J]. Cell death & disease, 2023, 14(7): 407.
[24]
Zhang C, Yue C, Herrmann A, et al. STAT3 activation-induced fatty acid oxidation in CD8+ T effector cells is critical for obesity-promoted breast tumor growth [J]. Cell metabolism, 2020, 31(1): 148-161.
[25]
田亚红, 高向东, 姚文兵, 等. CD4+ T细胞在肿瘤免疫治疗中的作用与应用研究进展 [J]. 药学进展, 2024, 48(6): 463-470.
[26]
Shu P, Liang H, Zhang J, et al. Reactive oxygen species formation and its effect on CD4+ T cell-mediated inflammation [J]. Frontiers in immunology, 2023, 14: 1199233.
[27]
Brown ZJ, Fu Q, Ma C, et al. Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC development [J]. Cell death & disease, 2018, 9(6): 620.
[28]
Yamada K, Saito M, Ando M, et al. Reduced number and immune dysfunction of CD4+ T cells in obesity accelerate colorectal cancer progression [J]. Cells, 2022, 12(1): 86.
[29]
Alnafea HM, Korish AA. Activation of the peroxisome proliferator-activated receptors (PPAR-α/γ) and the fatty acid metabolizing enzyme protein CPT1A by camel milk treatment counteracts the high-fat diet-induced nonalcoholic fatty liver disease [J]. PPAR research, 2021, 2021: 5558731.
[30]
Huang X, Liu B, Shen S. Lipid metabolism in breast cancer: from basic research to clinical application [J]. Cancers, 2025, 17(4): 650.
[31]
Cheng X, Tan X, Wang W, et al. Long-chain acylcarnitines induce senescence of invariant natural killer T cells in hepatocellular carcinoma [J]. Cancer research, 2023, 83(4): 582-594.
[32]
Kosaraju R, Guesdon W, Crouch MJ, et al. B Cell activity is impaired in human and mouse obesity and is responsive to an essential fatty acid upon murine influenza infection [J]. Journal of immunology (Baltimore, Md. : 1950), 2017, 198(12): 4738-4752.
[33]
Nedal TMV, Moen SH, Roseth IA, et al. Diet-induced obesity reduces bone marrow T and B cells and promotes tumor progression in a transplantable Vk*MYC model of multiple myeloma [J]. Scientific reports, 2024, 14(1): 3643.
[34]
Kennedy DE, Knight KL. Inhibition of B lymphopoiesis by adipocytes and IL-1-producing myeloid-derived suppressor cells [J]. Journal of Immunology, 2015, 195(6): 2666-2674.
[35]
Frasca D, Romero M, Diaz A, et al. Obesity accelerates age defects in B cells, and weight loss improves B cell function [J]. Immunity & ageing , 2023, 20(1): 35.
[36]
Hu T, Zhai J, Yang Z, et al. Myeloid-derived suppressor cells in cancer: mechanistic insights and targeted therapeutic innovations [J]. MedComm, 2025, 6(6): e70231.
[37]
He S, Zheng L, Qi C. Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy [J]. Molecular cancer, 2025, 24(1): 5.
[38]
Yang Z, Huo Y, Zhou S, et al. Cancer cell-intrinsic XBP1 drives immunosuppressive reprogramming of intratumoral myeloid cells by promoting cholesterol production [J]. Cell metabolism, 2022, 34(12): 2018-2035.
[39]
Li C, Wang G, Sivasami P, et al. Interferon-α-producing plasmacytoid dendritic cells drive the loss of adipose tissue regulatory T cells during obesity [J]. Cell metabolism, 2021, 33(8): 1610-1623.
[40]
Prendeville H, Lynch L. Diet, lipids, and antitumor immunity [J]. Cellular & molecular immunology, 2022, 19(3): 432-444.
[41]
Kichenadasse G, Miners JO, Mangoni AA, et al. Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer [J]. JAMA oncology, 2020, 6(4): 512-518.
[42]
Cortellini A, Bersanelli M, Buti S, et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable [J]. Journal for immunotherapy of cancer, 2019, 7(1): 57.
[43]
Costante F, Airola C, Santopaolo F, et al. Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma: Lights and shadows [J]. World journal of gastrointestinal oncology, 2022, 14(9): 1622-1636.
[44]
Mastrolonardo EV, Llerena P, De Ravin E, et al. Improved survival with elevated BMI following immune checkpoint inhibition across various solid tumor cancer types [J]. Cancer, 2025, 131(6): e35799.
[45]
Ihara Y, Sawa K, Imai T, et al. Immunotherapy and overall survival among patients with advanced non-small cell lung cancer and obesity [J]. JAMA network open, 2024, 7(8): e2425363.
[46]
Sbierski-Kind J, Grenkowitz S, Schlickeiser S, et al. Effects of caloric restriction on the gut microbiome are linked with immune senescence [J]. Microbiome, 2022, 10(1): 57.
[47]
Hirayama A, Kami K, Sugimoto M, et al. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry [J]. Cancer research, 2009, 69(11): 4918-4925.
[48]
Urasaki Y, Heath L, Xu CW. Coupling of glucose deprivation with impaired histone H2B monoubiquitination in tumors [J]. PloS one, 2012, 7(5): e36775.
[49]
Schild T, Wallisch P, Zhao Y, et al. Metabolic engineering to facilitate anti-tumor immunity [J]. Cancer cell, 2025, 43(3): 552-562.e9.
[50]
Hardie D G. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function [J]. Genes & development, 2011, 25(18): 1895-1908.
[51]
Ma EH, Poffenberger MC, Wong AHT, et al. The role of AMPK in T cell metabolism and function [J]. Current opinion in immunology, 2017, 46: 45-52.
[52]
范晓轩, 王娜, 朱丽花, 等. 肥胖相关肿瘤研究进展 [J/OL]. 中华肥胖与代谢病电子杂志, 2023, 9(3): 173-178.
[53]
Boulenouar S, Michelet X, Duquette D, et al. Adipose type one innate lymphoid cells regulate macrophage homeostasis through targeted cytotoxicity [J]. Immunity, 2017, 46(2): 273-286.
[54]
Michailidou Z, Gomez-Salazar M, Alexaki VI. Innate immune cells in the adipose tissue in health and metabolic disease [J]. Journal of innate immunity, 2022, 14(1): 4-30.
[55]
李涛, 张侃, 杨文雨, 等. 免疫检查点抑制剂CTLA-4在实体肿瘤治疗中的临床应用 [J]. 协和医学杂志, 2023, 14(3): 652-659.
[1] 陈斌雄, 谢铭. 袖状胃切除术与胃旁路术对肥胖合并T2DM的治疗效果[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(04): 461-466.
[2] 刘新锋, 邓煜麟, 刘孝德, 闫道先, 石双胜, 黄德成, 刘悦, 刘学斌, 许朋, 董传江. 肥大细胞免疫球蛋白样受体1在肾透明细胞癌中的表达及临床意义[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(04): 483-491.
[3] 谭廷武, 张平新, 夏成兴, 杨德林. 单细胞测序技术在前列腺癌免疫治疗中的应用现状及展望[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(04): 508-513.
[4] 孙晓容, 钟瑶, 张雯, 刘佳铭, 叶东樊. 肺癌免疫治疗并发脊髓炎救治成功一例[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(04): 657-659.
[5] 姚金平, 郭涛, 张逸辰, 常磊, 冯雨舟, 崔精, 陈建欢, 鲍传庆. 基于免疫微环境分析探讨FN1与DOCK2在结肠癌中的预后价值[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(04): 333-344.
[6] 吴振帼, 于岩波, 李延青. 内镜减重与代谢疗法的治疗新进展[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(03): 193-198.
[7] 洪敏, 许建峰, 丰陈. 内脏型肥胖对结直肠癌根治术患者术后感染并发症的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2025, 15(03): 199-204.
[8] 武世伦, 姚常玉, 许力, 狄治杉, 夏奇, 孙文兵, 孔健. 肿瘤相关巨噬细胞在肝细胞癌血管新生中的作用及研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(05): 388-391.
[9] 王美, 赵勇, 张健, 张俐娜, 丁健华, 曹煜. 基于CT测量肾周脂肪面积对Lap-ISR吻合口并发症的预测价值[J/OL]. 中华临床医师杂志(电子版), 2025, 19(05): 367-373.
[10] 尹巧英, 钱雅妮, 雷慧恩, 王石柳, 李婷婷, 尹瑞华, 卢璐. 针药结合治疗痰湿型多囊卵巢综合征肥胖:随机对照试验[J/OL]. 中华针灸电子杂志, 2025, 14(03): 99-103.
[11] 赖慧香, 林清然, 高丽莲. 中国肥胖代谢外科个案管理师专科化建设的挑战与机遇[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(03): 170-175.
[12] 张雯, 董志勇, 赵宛鄂, 王存川, 陈伟菊, 杨华. 护士对肥胖者态度的影响因素分析:基于问卷调查的多区域、多中心研究[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(03): 191-197.
[13] 胡曼, 林清然. 不同角度体重污名评估工具的研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(03): 213-221.
[14] 王思雨, 高丽莲, 于影, 杨华, 张雯, 林清然. 肥胖青少年接受减重代谢手术后骨骼健康的研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(03): 222-226.
[15] 南博, 拜云虎, 张宁, 杨雁灵. 肥胖与消化道肿瘤的研究进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(03): 240-248.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?