The Role of Lactate Dehydrogenase in Exploring the Immune Evasion in HCC Patients Who Underwent TACE: Implications for Clinical Application

Overview

Journal J Hepatocell Carcinoma

Date 2024 Oct 4

PMID 39364434

Authors

Yang Xie

Xiangyang Sun

Fubo Xie

Wencheng Jian

Qingliang Wang

Xiaochen Ma

Caixia Li

Kai Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: To examine the relationship between lactate dehydrogenase (LDH) levels and soluble programmed cell death-ligand 1 (sPD-L1) levels in hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE).

Methods: A total of 83 hCC patients participated in this study. Patients were categorized into subgroups based on their alpha-fetoprotein (AFP) levels, presence or absence of extrahepatic metastasis, vascular invasion, Barcelona Clinic Liver Cancer (BCLC) stage, tumor response, tumor size, and number LDH and sPD-L1 levels were compared before and after TACE (3, 7, and 30 days post-TACE).

Results: LDH and sPD-L1 levels were significantly higher at 3 and 7 days post-TACE than at baseline. Positive correlations were observed between changes in LDH levels and sPD-L1 levels at 3 and 7 days post-TACE. LDH levels were higher in patients with elevated AFP compared to those in the normal AFP group at 3 and 7 days post-TACE, in the stable disease (SD) group compared to complete response (CR) and partial response (PR) groups at 7 days post-TACE, and in those with tumor > 5 cm compared with those with tumor ≤ 5 cm at 3 and 7 days after TACE (all < 0.05). sPD-L1 levels were higher in patients with vascular invasion than those without vascular invasion at 3 and 7 days post-TACE, in the SD group compared to CR and PR groups at 3 and 7 days post-TACE, and in those with tumor > 5 cm compared to those with tumor < 5 cm at 3 and 7 days after TACE (all < 0.05).

Conclusion: A positive correlation was found between LDH expression and sPD-L1 levels, suggesting LDH as a potential biomarker for assessing immune status in HCC patients following TACE.

References

Xiaochen M, Xiangyang S, Fubo X, Wencheng J, Qingliang W, Yang X . The influence of transarterial chemoembolization on serum levels of soluble programed cell death ligand-1 in advanced hepatocellular carcinoma patients. Asia Pac J Clin Oncol. 2022; 18(5):e515-e523. DOI: 10.1111/ajco.13687. View

Ai L, Xu A, Xu J . Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond. Adv Exp Med Biol. 2020; 1248:33-59. DOI: 10.1007/978-981-15-3266-5_3. View

Zhuang G, Xie Y, Hong J, Lin S, Chen T, Fang W . Arterial chemoembolization for patients with hepatocellular carcinoma and elevated lactate dehydrogenase is associated with low survival: a cohort study. Infect Agent Cancer. 2022; 17(1):31. PMC: 9205044. DOI: 10.1186/s13027-022-00443-1. View

Faloppi L, Bianconi M, Memeo R, Casadei Gardini A, Giampieri R, Bittoni A . Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New. Biomed Res Int. 2016; 2016:7196280. PMC: 4903134. DOI: 10.1155/2016/7196280. View

Liao J, Xiao J, Zhou Y, Liu Z, Wang C . Effect of transcatheter arterial chemoembolization on cellular immune function and regulatory T cells in patients with hepatocellular carcinoma. Mol Med Rep. 2015; 12(4):6065-71. DOI: 10.3892/mmr.2015.4171. View

Goldman R, Kaplan N, Hall T . LACTIC DEHYDROGENASE IN HUMAN NEOPLASTIC TISSUES. Cancer Res. 1964; 24:389-99. View

Montasser A, Beaufrere A, Cauchy F, Bouattour M, Soubrane O, Albuquerque M . Transarterial chemoembolisation enhances programmed death-1 and programmed death-ligand 1 expression in hepatocellular carcinoma. Histopathology. 2020; 79(1):36-46. DOI: 10.1111/his.14317. View

Lacroix R, Rozeman E, Kreutz M, Renner K, Blank C . Targeting tumor-associated acidity in cancer immunotherapy. Cancer Immunol Immunother. 2018; 67(9):1331-1348. PMC: 11028141. DOI: 10.1007/s00262-018-2195-z. View

. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69(1):182-236. DOI: 10.1016/j.jhep.2018.03.019. View

10.

Faloppi L, Scartozzi M, Bianconi M, Svegliati Baroni G, Toniutto P, Giampieri R . The role of LDH serum levels in predicting global outcome in HCC patients treated with sorafenib: implications for clinical management. BMC Cancer. 2014; 14:110. PMC: 3930857. DOI: 10.1186/1471-2407-14-110. View

11.

He Q, Yang J, Jin Y . Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma. Front Immunol. 2022; 13:869993. PMC: 9043752. DOI: 10.3389/fimmu.2022.869993. View

12.

Pinato D, Murray S, Forner A, Kaneko T, Fessas P, Toniutto P . Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy. J Immunother Cancer. 2021; 9(9). PMC: 8487214. DOI: 10.1136/jitc-2021-003311. View

13.

Milross C, Tucker S, Mason K, Hunter N, Peters L, Milas L . The effect of tumor size on necrosis and polarographically measured pO2. Acta Oncol. 1997; 36(2):183-9. DOI: 10.3109/02841869709109228. View

14.

Mahipal A, Tella S, Kommalapati A, Lim A, Kim R . Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?. Cancers (Basel). 2019; 11(8). PMC: 6721326. DOI: 10.3390/cancers11081078. View

15.

Calderaro J, Rousseau B, Amaddeo G, Mercey M, Charpy C, Costentin C . Programmed death ligand 1 expression in hepatocellular carcinoma: Relationship With clinical and pathological features. Hepatology. 2016; 64(6):2038-2046. DOI: 10.1002/hep.28710. View

16.

Sun C, Mezzadra R, Schumacher T . Regulation and Function of the PD-L1 Checkpoint. Immunity. 2018; 48(3):434-452. PMC: 7116507. DOI: 10.1016/j.immuni.2018.03.014. View

17.

Wood D, Varela V, Palmquist M, Weber F . Serum lactic dehydrogenase and isoenzyme changes in clinical cancer. J Surg Oncol. 1973; 5(3):251-7. DOI: 10.1002/jso.2930050308. View

18.

Kim J, Chen D . Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016; 27(8):1492-504. DOI: 10.1093/annonc/mdw217. View

19.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

20.

Naruse T, Yanamoto S, Okuyama K, Ohmori K, Tsuchihashi H, Furukawa K . Immunohistochemical Study of PD-1/PD-L1 Axis Expression in Oral Tongue Squamous Cell Carcinomas: Effect of Neoadjuvant Chemotherapy on Local Recurrence. Pathol Oncol Res. 2019; 26(2):735-742. DOI: 10.1007/s12253-019-00606-3. View