Invariant Natural Killer T Cell Therapy Attenuates Systemic Inflammation and Improves Transarterial Chemoembolization Outcomes in Hepatocellular Carcinoma.

Authors

Xiaoxia Wang, Shuo Wang, Chendi Liang, Huili Wu, Songtao Liu, Jinhuan Wang, Jun Lu

Published in

Oncology research. Volume 34. Issue 9. Pages 26. Epub Aug 13, 2026.

Abstract

Background: Invariant natural killer T (iNKT) cells show promise as immunotherapeutic agents for solid tumors, and our prior study demonstrated that combining iNKT-cell therapy with transarterial chemoembolization (TACE) achieved a 58.3% objective response rate (ORR) in hepatocellular carcinoma (HCC). This study further examines iNKT-mediated immune modulation of post-TACE survival dynamics and associated prognostic biomarkers. Methods: Clinical data and peripheral blood samples were obtained from 77 HCC patients in Beijing you'an Hospital between 2018-2023, including 38 receiving TACE alone and 39 receiving combined iNKT-cell/TACE therapy. Serial measurements included: Hematological parameters; Liver function tests [alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin]; Inflammatory markers [C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR)]; Cytokine profiling [Interferon-gamma (IFN-γ), Interleukin-6 (IL-6), Interleukin-10 (IL-10)]. Potential Prognostic factors for progression-free survival (PFS) were identified through univariate/multivariate Cox regression. A risk-score model was derived using significant covariates from the multivariate analysis. Model performance was evaluated by time-dependent receiver operating characteristic (ROC) analysis [Area Under the Curve (AUC) calculation] and Kaplan-Meier survival stratification with log-rank testing. Results: The TACE group exhibited decreased lymphocytes but increased neutrophils/monocytes post-treatment, whereas iNKT + TACE maintained stable counts. Systemic inflammation indices [NLR/systemic immune-inflammation Index (SII)/systemic inflammation response index (SIRI)] rose significantly in TACE alone (all p < 0.05) but remained stable in iNKT + TACE. Cytokine profiling revealed reduced IL-6/IL-10 (p < 0.001/p = 0.012) and elevated IFN-γ/tumor necrosis factor-alpha (TNF-α) (p < 0.01/p < 0.001) in iNKT + TACE vs. TACE. Multivariate analysis identified lymphocyte count (HR = 0.18, 95%CI 0.04-0.76, p = 0.02), IL-6 (HR = 2.57, 95%CI 1.03-6.86, p = 0.04), and IFN-γ (HR = 0.14, 95%CI 0.02-0.98, p = 0.04) as independent PFS predictors. The risk model demonstrated strong discrimination (AUC = 0.891, 95%CI 0.73-1.00), with median PFS of 9.5 vs. 3.0 months for low- vs. high-risk groups (log-rank p < 0.01) in iNKT + TACE group. Conclusions: iNKT cell therapy stabilizes peripheral lymphocyte counts and attenuates TACE-induced inflammation in HCC. The combined evaluation of lymphocyte levels, IL-6, and IFN-γ represents a promising prognostic biomarker panel for PFS in iNKT + TACE-treated patients.

PMID:
42630714
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

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