|Table of Contents|

The expression level and clinical significance of OX40 and OX40L in hepatocellular carcinoma tissues

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2022 05
Page:
838-843
Research Field:
Publishing date:

Info

Title:
The expression level and clinical significance of OX40 and OX40L in hepatocellular carcinoma tissues
Author(s):
CHEN Xiaoqi1; RAN Xiaoke2; ZHAO Yunxia2; ZHAO Qing3; ZHANG Xin2; FAN Tianyu2; CHEN Xinju1
1.Department of Gastroenterology;3.Department of Scientific Research,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine，Henan Zhengzhou 450000,China；2.Henan University of Traditional Chinese Medicine,Henan Zhengzhou 450046,
Keywords:
hepatocellular carcinoma; OX40; OX40L; immunohistochemistry; prognosis
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2022.05.017
Abstract:
Objective:To investigate the expression level and clinical significance of OX40(CD134) and OX40L(CD134L) in hepatocellular carcinoma(HCC) tissues.Methods:Collecting 54 pathological tissues of patients with hepatocellular carcinoma with a clear pathological diagnosis.Immunohistochemical method was used to detect the expression of OX40 and OX40L in HCC tissues.The clinical significance in HCC and its correlation with prognosis based on clinical pathological data were also researched.Results:The positive rates of OX40 and OX40L protein expression in HCC tissues were 77.78% and 74.07% respectively,and there was a significant positive and strong correlation between both expression levels mentioned above(P=0.004).The expression level of OX40 was related to the degree of differentiation of patients（P＜0.05）,but not related to gender,age,tumor diameter,TNM stage,tumor thrombus formation,metastasis,number of tumors and AFP（P＞0.05）.The expression level of OX40L was related to the degree of differentiation and AFP（P＜0.05）,but not related to gender,age,tumor diameter,TNM stage,tumor thrombus formation,metastasis and tumor number（P＞0.05）.The cumulative survival rate and survival time of patients in the OX40 and OX40L positive expression group were higher than those in the negative expression group.It was also found that the expression level of OX40 was related to CD4+(P=0.036) and CD8+(P=0.003),while the expression level of OX40L was not related to CD4+(P=0.186) but related to CD8+(P=0.001).Conclusion:The expression levels of OX40 and OX40L are related to the occurrence,development and prognosis of HCC.Moreover,both expression levels may regulate the immune mechanism in body by stimulating CD4+ and CD8+ to inhibit the occurrence and development of HCC.

References:

[1] LLOVET JM,ZUCMAN-ROSSI J,PIKARSKY E,et al.Hepatocellular carcinoma［J］.Nat Rev Dis Primers,2016,14(2):16018.
[2] LABGAA I,TAFFP,MARTIN D,et al.Comparison of partial hepatectomy and transarterial chemoembolization in intermediate-stage hepatocellular carcinoma:A systematic review and Meta-analysis ［J］.Liver Cancer,2020,9(2):138-147.
[3] ANWANWAN D,SINGH SK,SINGH S,et al.Challenges in liver cancer and possible treatment approaches［J］.Biochim Biophys Acta Rev Cancer,2020,1873(1):188314.
[4] FU J,WANG H.Precision diagnosis and treatment of liver cancer in China［J］.Cancer Lett,2018,412:283-288.
[5] BRAHMER JR,TYKODI SS,CHOW LQ,et al.Safety and activity of anti-PD-L1 antibody in patients with advanced cancer［J］.N Engl J Med,2012,366(26):2455-2465.
[6] CALDERARO J,ROUSSEAU B,AMADDEO G,et al.Programmed death ligand 1 expression in hepatocellular carcinoma:Relationship With clinical and pathological features［J］.Hepatology,2016,64(6):2038-2046.
[7] CHENG AL,HSU C,CHAN SL,et al.Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma［J］.Hepatol,2020,72(2):307-319.
[8] KIM CG,KIM C,YOON SE,et al.Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma［J］.Hepatol,2020,74(2):350-359.
[9] PATERSON DJ,JEFFERIES WA,GREEN JR,et al.Antigens of activated rat T lymphocytes including a molecule of 50 000 Mr detected only on CD4 positive T blasts［J］.Mol Immunol,1987,24(12):1281-1290.
[10] LU X.OX40 and OX40L interaction in cancer［J］.Curr Med Chem,2021,28(28):5659-5673.
[11] WEBB GJ,HIRSCHFIELD GM,LANE PJ.OX40,OX40L and autoimmunity:a comprehensive review［J］.Clin Rev Allergy Immunol,2016,50(3):312-332.
[12] ISHII N,TAKAHASHI T,SOROOSH P,et al.OX40-OX40 ligand interaction in T-cell-mediated immunity and immunopathology［J］.Adv Immunol,2010,105:63-98.
[13] REDMOND WL,WEINBERG AD.Targeting OX40 and OX40L for the treatment of autoimmunity and cancer［J］.Crit Rev Immunol,2007,27(5):415-436.
[14] XIE K,XU L,WU H,et al.OX40 expression in hepatocellular carcinoma is associated with a distinct immune microenvironment,specific mutation signature,and poor prognosis［J］.Oncoimmunology,2018,7(4):e1404214.
[15] NOURI ROUZBAHANI F,SHIRKHODA M,MEMARI F,et al.Immunotherapy a new hope for cancer treatment:A review［J］.Pak J Biol Sci,2018,21(3):135-150.
[16] INTHAGARD J,EDWARDS J,ROSEWEIR AK.Immunotherapy:enhancing the efficacy of this promising therapeutic in multiple cancers［J］.Clin Sci(Lond),2019,133(2):181-193.
[17] TAN S,LI D,ZHU X.Cancer immunotherapy:Pros,cons and beyond［J］.Biomed Pharmacother,2020,124:109821.
[18] VOENA C,CHIARLE R.Advances in cancer immunology and cancer immunotherapy［J］.Discov Med,2016,21(114):125-133.
[19] LINCH SN,MCNAMARA MJ,REDMOND WL.OX40 agonists and combination immunotherapy:Putting the pedal to the metal［J］.Front Oncol,2015,5:34.
[20] ASPESLAGH S,POSTEL-VINAY S,RUSAKIEWICZ S,et al.Rationale for anti-OX40 cancer immunotherapy［J］.Eur J Cancer,2016,52:50-66.
[21] BUCHAN SL,ROGEL A,AL-SHAMKHANI A.The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy［J］.Blood,2018,131(1):39-48.
[22] FU Y,LIN Q,ZHANG Z,et al.Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity［J］.Acta Pharm Sin B,2020,10(3):414-433.
[23] REDMOND WL,LINCH SN,KASIEWICZ MJ.Combined targeting of costimulatory(OX40) and coinhibitory(CTLA-4) pathways elicits potent effector T cells capable of driving robust antitumor immunity［J］.Cancer Immunol Res,2014,2(2):142-153.
[24] MASSARELLI E,LAM VK,PARRA ER,et al.High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer［J］.J Immunother Cancer,2019,7(1):351.
[25] OHMURA H,YAMAGUCHI K,HANAMURA F,et al.OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody［J］.Br J Cancer,2020,122(10):1507-1517.
[26] CHONAN M,SAITO R,SHOJI T,et al.CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models［J］.Neuro Oncol,2015,17(11):1453-1462.
[27] SARFF M,EDWARDS D,DHUNGEL B,et al.OX40(CD134) expression in sentinel lymph nodes correlates with prognostic features of primary melanomas［J］.Am J Surg,2008,195(5):621-625.
[28] REDMOND WL,WEINBERG AD.Targeting OX40 and OX40L for the treatment of autoimmunity and cancer［J］.Crit Rev Immunol,2007,27(5):415-436.
[29] SOROOSH P,INE S,SUGAMURA K,et al.OX40-OX40 ligand interaction through T cell-T cell contact contributes to CD4 T cell longevity［J］.Immunol,2006,176(10):5975-5987.
[30] CROFT M,SO T,DUAN W,et al.The significance of OX40 and OX40L to T-cell biology and immune disease［J］.Immunol Rev,2009,229(1):173-191.
[31] WEINBERG AD,RIVERA MM,PRELL R,et al.Engagement of the OX-40 receptor in vivo enhances antitumor immunity［J］.Immunol,2000,164(4):2160-2169.
[32] ALI SA,AHMAD M,LYNAM J,et al.Anti-tumour therapeutic efficacy of OX40L in murine tumour model.Vaccine［J］.2004,22(27-28):3585-3594.
[33] ROSENBERG SA,YANG JC,SHERRY RM,et al.Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy［J］.Clin Cancer Res,2011,17(13):4550-4557.

Memo

Memo:
国家科技重大专项-艾滋病和病毒性肝炎等重大传染病防治项目（编号：2018ZX10303502-001）；河南省中医药科学研究专项课题重点项目（编号：2018JDZX110）；河南省中医药科学研究专项课题（编号：2017JDZX029）；河南省特色骨干学科中医学学科建设项目（编号：STG-ZYXKY-2020019）
Last Update: 2022-01-27