Open Access

ARTICLE

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

Xiaoxia Wang^1,2,#, Shuo Wang^1,2,#, Chendi Liang^1,2,#, Huili Wu^1,2, Songtao Liu^1,2, Jinhuan Wang^1,2, Jun Lu^1,2,*
1 Department of Medical Oncology, Beijing You An Hospital, Capital Medical University, Beijing, China
2 Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
* Corresponding Author: Jun Lu. Email:
# These authors contributed equally to this work
(This article belongs to the Special Issue: Advancements in Hepatocellular Carcinoma Treatment)

Oncology Research https://doi.org/10.32604/or.2026.082815

Received 29 March 2026; Accepted 26 June 2026; Published online 23 July 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.

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Keywords

Invariant natural killer T; inflammation; hepatocellular carcinoma; transarterial chemoembolization

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