Correlation Between PD-1/CTLA-4 Expressions with C linicopathological Features and Prognosis of Osteosarcoma Patients

YAN Guangning; YU Ling; LAI Xuwen; YE Danli; WANG Wei; WANG Zhuocai

doi:10.3971/j.issn.1000-8578.2023.22.0483

Cancer Research on Prevention and Treatment > 2023 > 50(1): 63-68. > DOI: 10.3971/j.issn.1000-8578.2023.22.0483

YAN Guangning, YU Ling, LAI Xuwen, YE Danli, WANG Wei, WANG Zhuocai. Correlation Between PD-1/CTLA-4 Expressions with C linicopathological Features and Prognosis of Osteosarcoma Patients[J]. Cancer Research on Prevention and Treatment, 2023, 50(1): 63-68. DOI: 10.3971/j.issn.1000-8578.2023.22.0483

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Correlation Between PD-1/CTLA-4 Expressions with C linicopathological Features and Prognosis of Osteosarcoma Patients

Department of Pathology, General Hospital of Southern Theatre Command, Guangzhou 510010, China

Funding:

Youth Program of National Natural and Science Foundation of China 81802962

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Corresponding author:
WANG Zhuocai, E-mail: wangzcmail@163.com
Received Date: May 04, 2022
Revised Date: July 20, 2022
Available Online: January 12, 2024

Graphical Abstract

Abstract

Abstract

Objective
To explore the expression of PD-1 and CTLA-4 in osteosarcoma and their clinical significance.
Methods
Fifty-eight cases of osteosarcoma encountered from 2007 to 2016 were enrolled. The expression levels of PD-1 and CTLA-4 were detected through immunohistochemistry (EnVision method).
Results
PD-1 was positively expressed in 31 (53.4%) cases and negatively expressed in 27 (46.6%) cases. CTLA-4 was positively expressed in 19 (32.8%) cases and negatively expressed in 39 (67.2%) cases. A total of 12 (20.7%) cases were PD-1 and CTLA-4 double positive, whereas 20 (34.5%) cases were double negative, and 26 (44.8%) cases were single positive. The positive expression of PD-1 was correlated with neoadjuvant chemotherapy, tumor metastasis and relapse, and shortened survival time (P < 0.05). The positive expression of CTLA-4 was partly related with late Ennecking stage (P=0.051). Double positive expression was related to the highest tumor metastasis and relapse rates and the worst prognosis (P < 0.05), compared with double negative and single positive expression.
Conclusion
Positive expression of PD-1 and CTLA-4 in osteosarcoma is associated with worse prognosis, whereas double positive expression is associated with the highest tumor relapse and metastasis rates and shortest survival time. These results are potential valuable references for osteosarcoma immunotherapy.
- Osteosarcoma,
- PD-1,
- CTLA-4,
- Prognosis

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Competing interests: The authors declare that they have no competing interests.

References (20)

References

[1]	Cesne AL, Marec-Berard P, Blay JY, et al. Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study[J]. Euro J Cancer, 2019, 119: 151-157. doi: 10.1016/j.ejca.2019.07.018
[2]	高峰, 洪亚珍, 陈晨, 等. 癌症治疗的新兴免疫靶点及相关研究进展[J]. 中国肿瘤临床, 2020, 47(19): 1001-1006. doi: 10.3969/j.issn.1000-8179.2020.19.736 Gao F, Hong YZ, Chen C, et al. Current status of emerging targets for cancer immunotherapy[J]. Zhongguo Zhong Liu Lin Chuang, 2020, 47(19): 1001-1006. doi: 10.3969/j.issn.1000-8179.2020.19.736
[3]	Karpathiou G, Chauleur C, Mobarki M, et al. The immune checkpoints CTLA-4 and PD-L1 in carcinomas of the uterine cervix[J]. PatholRes Prac, 2019, 216(1): 152782.
[4]	Wang SD, Li HY, Li BH, et al. The role of CTLA-4 and PD-1 in anti-tumor immune response and their potential efficacy against osteosarcoma[J]. Int Immunopharmacol, 2016, 38: 81-89. doi: 10.1016/j.intimp.2016.05.016
[5]	Que Y, Fang Z, Guan Y, et al. LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival[J]. Cancer Biol Med, 2019, 16(2): 331-340. doi: 10.20892/j.issn.2095-3941.2018.0306
[6]	Datar I, Sanmamed MF, Wang J, et al. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non-Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis[J]. Clin Cancer Res, 2019, 25(15): 4663-4673. doi: 10.1158/1078-0432.CCR-18-4142
[7]	周舸, 谢丽平, 林涛发, 等. 肝细胞癌组织中程序性死亡受体1和T淋巴细胞免疫球蛋白黏蛋白3的表达及意义[J]. 临床肝胆病杂志, 2020, 36(11): 2450-2455. doi: 10.3969/j.issn.1001-5256.2020.11.011 Zhou G, Xie LP, Lin TF, et al. Expression and significance of programmed death-1 and T-cell immunoglobulin-and mucin domain-3-contai-ning molecule 3 in hepatocellular carcinoma[J]. Lin Chuang Gan Dan Bing Za Zhi, 2020, 36(11): 2450-2455. doi: 10.3969/j.issn.1001-5256.2020.11.011
[8]	蓝瑞隆, 傅冷西, 陈瑞庆, 等. 骨肉瘤程序性死亡因子配体1的表达及临床意义[J]. 国际骨科学杂志, 2018, 39(4): 245-249. doi: 10.3969/j.issn.1673-7083.2018.04.012 Lan RL, Fu LX, Chen RQ, et al. PD-L1 expression in human osteosarcoma and its clinical significance[J]. Guo Ji Gu Ke Xue Za Zhi, 2018, 39(4): 245-249. doi: 10.3969/j.issn.1673-7083.2018.04.012
[9]	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. doi: 10.1007/s00432-020-03242-6
[10]	Zheng W, Xiao H, Liu H, et al. Expression of programmed death 1 is correlated with progression of osteosarcoma[J]. APMIS, 2015, 123(2): 102-107. doi: 10.1111/apm.12311
[11]	胡越皓, 鲍其远, 沈宇辉, 等. 程序性死亡受体1及其配体抑制剂治疗骨肉瘤的研究进展[J]. 国际骨科学杂志, 2019, 40(5): 263-267. doi: 10.3969/j.issn.1673-7083.2019.05.002 Hu YH, Bao QY, Shen YH, et al. Progress in the treatment of osteosarcoma with programmed death receptor 1 and its ligand inhibitors[J]. Guo Ji Gu Ke Xue Za Zhi, 2019, 40: 263-267. doi: 10.3969/j.issn.1673-7083.2019.05.002
[12]	Li Y, Liu J, Gao L, et al. Targeting the tumor microenvironment to overcome immune checkpoint blockade therapy resistance[J]. Immunol Lett, 2020, 220: 88-96. doi: 10.1016/j.imlet.2019.03.006
[13]	Sudo S, Kajiya H, Okano S, et al. Cisplatin-induced programmed cell death ligand-2 expression is associated with metastasis ability in oral squamous cell carcinoma[J]. Cancer Sci, 2020, 111(4): 1113-1123. doi: 10.1111/cas.14336
[14]	Verma N, Burns SO, Walker LSK, et al. Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations[J]. Clin Exp Immunol, 2017, 190(1): 1-7. doi: 10.1111/cei.12997
[15]	Zhang C, Chen J, Song Q, et al. Comprehensive analysis of CTLA-4 in the tumor immune microenvironment of 33 cancer types[J]. Int Immunopharmacol, 2020, 85: 106633. doi: 10.1016/j.intimp.2020.106633
[16]	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. doi: 10.3892/or.2013.2224
[17]	Liu Y, Zheng P. Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy[J]. Trends Pharmacol Sci, 2019, 41(1): 4-12.
[18]	Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma[J]. N Engl J Med, 2015, 372(26): 2521-2532. doi: 10.1056/NEJMoa1503093
[19]	Patel SP, Othus M, Chae YK, et al. A PhaseⅡ Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609) in Patients with Nonpancreatic Neuroendocrine Tumors[J]. Clin Cancer Res, 2020, 26(10): 2290-2296. doi: 10.1158/1078-0432.CCR-19-3356
[20]	Lussier DM, Johnson JL, Hingorani P, et al. Combination immunotherapy with alpha-CTLA-4 and alpha-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma[J]. J Immunother Cancer, 2015, 3: 21. doi: 10.1186/s40425-015-0067-z

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[6]	HU Lili, YIN Yanjun, ZHONG Wenjuan, QIU Feng. miR-200c Enhances Sensitivity of Lung Cancer Cell A549 to Paclitaxel and Gefitinib and Related Mechanism[J]. Cancer Research on Prevention and Treatment, 2015, 42(08): 760-764. DOI: 10.3971/j.issn.1000-8578.2015.08.003
[7]	CAO Xinmei, ZHANG Daiquan, XIA Jiyi, WANG Xu, GAO Yan, XIONG Wei. Effects of HER2 shRNA on Chemotherapy Sensitivity of Mouse Lewis Cells[J]. Cancer Research on Prevention and Treatment, 2014, 41(05): 366-368. DOI: 10.3971/j.issn.1000-8578.2014.05.004
[8]	Yang Qingshan, Liu Yuanyuan, Jiang Lipeng. Effect of Expression Vector of Human BAG-1 Gene on Radio-sensitivity of Lung Adenocarcinoma Cells[J]. Cancer Research on Prevention and Treatment, 2012, 39(02): 127-129. DOI: 10.3971/j.issn.1000-8578.2012.02.002
[9]	FANG Chuan, TAN Yan-li, WANG Jia-liang, SHI Yan-fang, SHAN Xiao-song, LI Wei. Primary Culture and Drug Sensitivity of Human Glioma Cells[J]. Cancer Research on Prevention and Treatment, 2010, 37(12): 1380-1382. DOI: 10.3971/j.issn.1000-8578.2010.12.012
[10]	ZHANG Wei, GU Min. Geldanamycin Sensitizes Human Breast Cancer Cells to Adriamycin both in vitro and in vivo[J]. Cancer Research on Prevention and Treatment, 2010, 37(10): 1109-1112. DOI: 10.3971/j.issn.1000-8578.2010.10.004

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Correlation Between PD-1/CTLA-4 Expressions with C linicopathological Features and Prognosis of Osteosarcoma Patients