骨肉瘤免疫微环境及其免疫治疗临床转化研究进展

doi:10.3969/j.issn.1674-8115.2024.07.002

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (7): 814-821.doi: 10.3969/j.issn.1674-8115.2024.07.002

• 转化医学研究前沿进展专题 • 上一篇下一篇

骨肉瘤免疫微环境及其免疫治疗临床转化研究进展

胡飞¹(), 蔡晓涵², 程睿³, 季诗雨⁴, 苗嘉欣⁵, 朱晏⁶, 范广建⁷()

^1.上海交通大学医学院附属仁济医院骨关节外科，上海 200001
^2.上海交通大学医学院附属仁济医院中心实验室，上海 200127
^3.上海交通大学医学院附属新华医院超声科，上海 200092
^4.上海交通大学医学院附属第一人民医院泌尿外科，上海 200080
^5.上海交通大学医学院附属新华医院核医学科，上海 200092
^6.上海交通大学医学院附属仁济医院上海市肿瘤研究所，肿瘤系统医学全国重点实验室，上海 200032
^7.上海交通大学医学院附属第一人民医院疑难疾病精准研究中心，上海 201600

收稿日期:2023-12-28 接受日期:2024-05-22 出版日期:2024-07-28 发布日期:2024-07-28
通讯作者: 范广建 E-mail:hufei200009@163.com;gjfan@shsmu.edu.cn
作者简介:胡　飞（1999—），男，硕士生；电子信箱：hufei200009@163.com。
基金资助:
国家自然科学基金(32270749);山东省泰山学者工程（青年专家计划）(tsqn202306197)

Progress in translational research on immunotherapy for osteosarcoma

HU Fei¹(), CAI Xiaohan², CHENG Rui³, JI Shiyu⁴, MIAO Jiaxin⁵, ZHU Yan⁶, FAN Guangjian⁷()

^1.Department of Bone and Joint Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
^2.Central Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
^3.Department of Ultrasound, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
^4.Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
^5.Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
^6.State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
^7.Precision Research Center for Difficult Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China

Received:2023-12-28 Accepted:2024-05-22 Online:2024-07-28 Published:2024-07-28
Contact: FAN Guangjian E-mail:hufei200009@163.com;gjfan@shsmu.edu.cn
Supported by:
National Natural Science Foundation of China(32270749);Taishan Scholar Project of Shandong Province (Young Expert Program)(tsqn202306197)

摘要/Abstract

摘要：

骨肉瘤（osteosarcoma）是儿童和青少年常见的原发性恶性骨肿瘤，因其高复发率和高转移率的特点，在治疗上面临极大的挑战。传统的治疗手段，包括手术、放射治疗（放疗）和化学治疗（化疗），能在一定程度上缓解患者的症状，但如何提高患者的长期生存率仍然是亟待解决的难题。随着免疫治疗的不断发展，近年来对肿瘤免疫微环境的研究以及免疫治疗策略的应用均取得了突破性的进展，为骨肉瘤的治疗提供了新的视角。目前，免疫治疗的策略包括肿瘤疫苗、靶向细胞因子、免疫检查点抑制、过继细胞疗法以及联合治疗等。以上策略旨在增强机体免疫反应、克服免疫耐受和防止免疫逃逸，显著提升患者的免疫应答能力。该文系统介绍骨肉瘤的免疫微环境，深入分析免疫微环境的特征，详细阐述免疫治疗在骨肉瘤临床转化研究中的最新进展。深入理解骨肉瘤的免疫特性和相应的治疗方法，有助于为患者提供个性化治疗方案，从而提高其生存率和改善预后。

关键词: 骨肉瘤, 肿瘤免疫微环境, 免疫治疗, 临床转化

Abstract:

Osteosarcoma is a common primary malignant bone tumor in adolescents and children, characterized by a high recurrence rate and metastasis, making its treatment extremely challenging. Traditional treatment modalities, including surgery, radiation therapy, and chemotherapy, can alleviate symptoms to some extent, but improving long-term survival rates remains a pressing issue. With the continuous development of immunotherapy, breakthroughs have been made in the research of tumor immune microenvironment and the application of immunotherapy in recent years, providing new perspectives and strategies for osteosarcoma treatment. Currently, immunotherapy strategies include tumor vaccines, targeted cytokines, immune checkpoint inhibition, adoptive cell therapy, combination therapy, etc., significantly enhancing patient immune responses from the aspects of boosting immunity, overcoming immune tolerance, and preventing immune evasion, thereby effectively improving the patients′ survival rates and prognosis. This review aims to systematically introduce the immune microenvironment of osteosarcoma and discuss the latest advances in immunotherapy in clinical translational research of osteosarcoma. By deeply understanding the immune characteristics of osteosarcoma and corresponding treatment methods, it is hopeful to provide more effective strategies for personalized treatment, contributing to the improvement of the patients′ survival rates and prognosis.

Key words: osteosarcoma, tumor immune microenvironment (TIME), immunotherapy, clinical translation

中图分类号:

R738.1

胡飞, 蔡晓涵, 程睿, 季诗雨, 苗嘉欣, 朱晏, 范广建. 骨肉瘤免疫微环境及其免疫治疗临床转化研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(7): 814-821.

HU Fei, CAI Xiaohan, CHENG Rui, JI Shiyu, MIAO Jiaxin, ZHU Yan, FAN Guangjian. Progress in translational research on immunotherapy for osteosarcoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 814-821.

参考文献 69

1	ZHAO X, WU Q R, GONG X Q, et al. Osteosarcoma: a review of current and future therapeutic approaches[J]. Biomed Eng Online, 2021, 20(1): 24.
2	BERNTHAL N M, FEDERMAN N, EILBER F R, et al. Long-term results (>25 years) of a randomized, prospective clinical trial evaluating chemotherapy in patients with high-grade, operable osteosarcoma[J]. Cancer, 2012, 118(23): 5888-5893.
3	XU Y, SHI F Q, ZHANG Y T, et al. Twenty-year outcome of prevalence, incidence, mortality and survival rate in patients with malignant bone tumors[J]. Int J Cancer, 2024, 154(2): 226-240.
4	MOUKENGUE B, LALLIER M, MARCHANDET L, et al. Origin and therapies of osteosarcoma[J]. Cancers, 2022, 14(14): 3503.
5	ZHU T Y, HAN J, YANG L, et al. Immune microenvironment in osteosarcoma: components, therapeutic strategies and clinical applications[J]. Front Immunol, 2022, 13: 907550.
6	ZHOU Y, YANG D, YANG Q C, et al. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma[J]. Nat Commun, 2020, 11(1): 6322.
7	CERSOSIMO F, LONARDI S, BERNARDINI G, et al. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy[J]. Int J Mol Sci, 2020, 21(15): 5207.
8	刘净峰, 徐鸿锋, 刘巍峰. 骨肉瘤驱动基因与免疫微环境及靶向治疗的研究进展[J]. 中国骨与关节杂志, 2024, 13(5): 390-395.
	LIU J F, XU H F, LIU W F. Research advances on osteosarcoma driver genes, immune microenvironment, and targeted therapy[J]. Chinese Journal of Bone and Joint, 2024, 13(5): 390-395.
9	HUANG Q S, LIANG X, REN T T, et al. The role of tumor-associated macrophages in osteosarcoma progression-therapeutic implications[J]. Cell Oncol, 2021, 44(3): 525-539.
10	TIAN H L, CAO J J, LI B W, et al. Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment[J]. Bone Res, 2023, 11(1): 11.
11	HOU C H, LU M, LEI Z X, et al. HMGB1 positive feedback loop between cancer cells and tumor-associated macrophages promotes osteosarcoma migration and invasion[J]. Lab Invest, 2023, 103(5): 100054.
12	WOLF-DENNEN K, GORDON N, KLEINERMAN E S. Exosomal communication by metastatic osteosarcoma cells modulates alveolar macrophages to an M2 tumor-promoting phenotype and inhibits tumoricidal functions[J]. Oncoimmunology, 2020, 9(1): 1747677.
13	CHENG Z H, WANG L Q, WU C H, et al. Tumor-derived exosomes induced M2 macrophage polarization and promoted the metastasis of osteosarcoma cells through Tim-3[J]. Arch Med Res, 2021, 52(2): 200-210.
14	ANAND N, PEH K H, KOLESAR J M. Macrophage repolarization as a therapeutic strategy for osteosarcoma[J]. Int J Mol Sci, 2023, 24(3): 2858.
15	RAGGI C, MOUSA H S, CORRENTI M, et al. Cancer stem cells and tumor-associated macrophages: a roadmap for multitargeting strategies[J]. Oncogene, 2016, 35(6): 671-682.
16	LIN J T, XU A K, JIN J K, et al. MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression[J]. Oncoimmunology, 2022, 11(1): 2024941.
17	KALLURI R, LEBLEU V S. The biology,function,and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977.
18	ZHANG L, YU D H. Exosomes in cancer development, metastasis, and immunity[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(2): 455-468.
19	WANG J, ZHANG H L, SUN X, et al. Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients[J]. J Nanobiotechnology, 2020, 18(1): 151.
20	PU F F, CHEN F X, ZHANG Z C, et al. Information transfer and biological significance of neoplastic exosomes in the tumor microenvironment of osteosarcoma[J]. Onco Targets Ther, 2020, 13: 8931-8940.
21	TANG J X, HE J Y, FENG C Y, et al. Exosomal miRNAs in osteosarcoma: biogenesis and biological functions[J]. Front Pharmacol, 2022, 13: 902049.
22	DYSON K A, STOVER B D, GRIPPIN A, et al. Emerging trends in immunotherapy for pediatric sarcomas[J]. J Hematol Oncol, 2019, 12(1): 78.
23	ZHONG R, LING X, CAO S, et al. Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers[J]. ESMO Open, 2022, 7(1): 100334.
24	YU J F, SUN H, CAO W J, et al. Research progress on dendritic cell vaccines in cancer immunotherapy[J]. Exp Hematol Oncol, 2022, 11(1): 3.
25	ASSI T, WATSON S, SAMRA B, et al. Targeting the VEGF pathway in osteosarcoma[J]. Cells, 2021, 10(5): 1240.
26	DUFFAUD F, MIR O, BOUDOU-ROUQUETTE P, et al. Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study[J]. Lancet Oncol, 2019, 20(1): 120-133.
27	DAVIS L E, BOLEJACK V, RYAN C W, et al. Randomized double-blind phase Ⅱ study of regorafenib in patients with metastatic osteosarcoma[J]. J Clin Oncol, 2019, 37(16): 1424-1431.
28	DUFFAUD F, BLAY J Y, LE CESNE A, et al. Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase Ⅱ study[J]. Br J Cancer, 2023, 129(12): 1940-1948.
29	TIAN Z C, WANG J Q, GE H. Apatinib ameliorates doxorubicin-induced migration and cancer stemness of osteosarcoma cells by inhibiting Sox2 via STAT3 signalling[J]. J Orthop Translat, 2020, 22: 132-141.
30	LIU K S, REN T T, HUANG Y, et al. Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma[J]. Cell Death Dis, 2017, 8(8): e3015.
31	XIE L, XU J, SUN X, et al. Apatinib for advanced osteosarcoma after failure of standard multimodal therapy: an open label phase Ⅱ clinical trial[J]. Oncologist, 2019, 24(7): e542-e550.
32	ZHANG X, PAN Q Z, PENG R Q, et al. A phase Ⅱ study of surufatinib in patients with osteosarcoma and soft tissue sarcoma who have experienced treatment failure with standard chemotherapy[J]. J Clin Oncol, 2023, 41(16_suppl): e23540.
33	YU L F, FAN G T, WANG Q Y, et al. In vivo self-assembly and delivery of VEGFR2 siRNA-encapsulated small extracellular vesicles for lung metastatic osteosarcoma therapy[J]. Cell Death Dis, 2023, 14(9): 626.
34	HAVEL J J, CHOWELL D, CHAN T A. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy[J]. Nat Rev Cancer, 2019, 19(3): 133-150.
35	YI M, NIU M K, XU L P, et al. Regulation of PD-L1 expression in the tumor microenvironment[J]. J Hematol Oncol, 2021, 14(1): 10.
36	HASHIMOTO K, NISHIMURA S, AKAGI M. Characterization of PD-1/PD-L1 immune checkpoint expression in osteosarcoma[J]. Diagnostics, 2020, 10(8): 528.
37	TODA Y, KOHASHI K, YAMADA Y, et al. PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions[J]. J Cancer Res Clin Oncol, 2020, 146(10): 2607-2620.
38	DHUPKAR P, GORDON N, STEWART J, et al. Anti-PD-1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases[J]. Cancer Med, 2018, 7(6): 2654-2664.
39	ZHANG M, CHEN L, LI Y, et al. PD‑L1/PD‑1 axis serves an important role in natural killer cell‑induced cytotoxicity in osteosarcoma[J]. Oncol Rep, 2019, 42(5): 2049-2056.
40	BOYE K, LONGHI A, GUREN T, et al. Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial[J]. Cancer Immunol Immunother, 2021, 70(9): 2617-2624.
41	WEN Y, TANG F, TU C Q, et al. Immune checkpoints in osteosarcoma: recent advances and therapeutic potential[J]. Cancer Lett, 2022, 547: 215887.
42	XIE L, XU J, SUN X, et al. Apatinib plus camrelizumab (anti-PD1 therapy, SHR-1210) for advanced osteosarcoma (APFAO) progressing after chemotherapy: a single-arm, open-label, phase 2 trial[J]. J Immunother Cancer, 2020, 8(1): e000798.
43	SZNOL M, MELERO I. Revisiting anti-CTLA-4 antibodies in combination with PD-1 blockade for cancer immunotherapy[J]. Ann Oncol, 2021, 32(3): 295-297.
44	ROY D, GILMOUR C, PATNAIK S, et al. Combinatorial blockade for cancer immunotherapy: targeting emerging immune checkpoint receptors[J]. Front Immunol, 2023, 14: 1264327.
45	BAGCHI S, YUAN R, ENGLEMAN E G. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance[J]. Annu Rev Pathol, 2021, 16: 223-249.
46	YUAN J H, JIA J Y, WU T L, et al. Long intergenic non-coding RNA DIO3OS promotes osteosarcoma metastasis via activation of the TGF-β signaling pathway: a potential diagnostic and immunotherapeutic target for osteosarcoma[J]. Cancer Cell Int, 2023, 23(1): 215.
47	XIE L, CHEN C L, LIANG X, et al. Expression and clinical significance of various checkpoint molecules in advanced osteosarcoma: possibilities for novel immunotherapy[J]. Orthop Surg, 2023, 15(3): 829-838.
48	ZHANG Y M, GAN W Y, RU N, et al. Comprehensive multi-omics analysis reveals m7G-related signature for evaluating prognosis and immunotherapy efficacy in osteosarcoma[J]. J Bone Oncol, 2023, 40: 100481.
49	SCHULTZ L. Chimeric antigen receptor T cell therapy for pediatric B-ALL: narrowing the gap between early and long-term outcomes[J]. Front Immunol, 2020, 11: 1985.
50	LI S Z, ZHANG H, SHANG G N. Current status and future challenges of CAR-T cell therapy for osteosarcoma[J]. Front Immunol, 2023, 14: 1290762.
51	CORTI C, VENETIS K, SAJJADI E, et al. CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress[J]. Expert Opin Investig Drugs, 2022, 31(6): 593-605.
52	KACZANOWSKA S, MURTY T, ALIMADADI A, et al. Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy[J]. Cancer Cell, 2024, 42(1): 35-51.e8.
53	ZHU J W, SIMAYI N, WAN R X, et al. CAR T targets and microenvironmental barriers of osteosarcoma[J]. Cytotherapy, 2022, 24(6): 567-576.
54	MENSALI N, KÖKSAL H, JOAQUINA S, et al. ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma[J]. Nat Commun, 2023, 14(1): 3375.
55	MOONAT H, HUANG G X, DHUPKAR P, et al. Combination of interleukin-11Rα chimeric antigen receptor T-cells and programmed death-1 blockade as an approach to targeting osteosarcoma cells in vitro[J]. Cancer Transl Med, 2017, 3(4): 139.
56	LUSSIER D M, JOHNSON J L, HINGORANI P, et al. Combination immunotherapy with α-CTLA-4 and α-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma[J]. J Immunother Cancer, 2015, 3: 21.
57	D'ANGELO S P, MAHONEY M R, VAN TINE B A, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials[J]. Lancet Oncol, 2018, 19(3): 416-426.
58	KAWANO M, ITONAGA I, IWASAKI T, et al. Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma[J]. Oncol Rep, 2013, 29(3): 1001-1006.
59	KRUPKA C, KUFER P, KISCHEL R, et al. Blockade of the PD-1/PD-L1 axis augments lysis of AML cells by the CD33/CD3 BiTE antibody construct AMG 330: reversing a T-cell-induced immune escape mechanism[J]. Leukemia, 2016, 30(2): 484-491.
60	SUN C, DOTTI G, SAVOLDO B. Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies[J]. Blood, 2016, 127(26): 3350-3359.
61	WANG Z, LI B H, REN Y Q, et al. T-cell-based immunotherapy for osteosarcoma: challenges and opportunities[J]. Front Immunol, 2016, 7: 353.
62	CHAPUIS A G, ROBERTS I M, THOMPSON J A, et al. T-cell therapy using interleukin-21-primed cytotoxic T-cell lymphocytes combined with cytotoxic T-cell lymphocyte antigen-4 blockade results in long-term cell persistence and durable tumor regression[J]. J Clin Oncol, 2016, 34(31): 3787-3795.
63	CURRAN M A, MONTALVO W, YAGITA H, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors[J]. Proc Natl Acad Sci U S A, 2010, 107(9): 4275-4280.
64	YU A L, GILMAN A L, OZKAYNAK M F, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma[J]. N Engl J Med, 2010, 363(14): 1324-1334.
65	ZHU W H, MAO X Z, WANG W C, et al. Anti-ganglioside GD2 monoclonal antibody synergizes with cisplatin to induce endoplasmic reticulum-associated apoptosis in osteosarcoma cells[J]. Pharmazie, 2018, 73(2): 80-86.
66	THANINDRATARN P, DEAN D C, NELSON S D, et al. Advances in immune checkpoint inhibitors for bone sarcoma therapy[J]. J Bone Oncol, 2019, 15: 100221.
67	YAMADA N, HATA M, OHYAMA H, et al. Immunotherapy with interleukin-18 in combination with preoperative chemotherapy with ifosfamide effectively inhibits postoperative progression of pulmonary metastases in a mouse osteosarcoma model[J]. Tumour Biol, 2009, 30(4): 176-184.
68	HE X J, LIN H Q, YUAN L, et al. Combination therapy with L-arginine and α-PD-L1 antibody boosts immune response against osteosarcoma in immunocompetent mice[J]. Cancer Biol Ther, 2017, 18(2): 94-100.
69	KAWANO M, TANAKA K, ITONAGA I, et al. Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma[J]. Oncol Lett, 2016, 11(3): 2169-2175.

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[14]	李夏伊，郑磊贞. 程序性死亡蛋白 1/程序性死亡配体 1抑制剂在晚期胃癌治疗中的应用[J]. 上海交通大学学报（医学版）, 2018, 38(10): 1259-.
[15]	夏莉，王月英 . 嵌合抗原受体 T 细胞疗法及其在血液肿瘤免疫治疗中的应用[J]. 上海交通大学学报（医学版）, 2017, 37(6): 822-.

骨肉瘤免疫微环境及其免疫治疗临床转化研究进展

Progress in translational research on immunotherapy for osteosarcoma

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