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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

This article is part of the Research TopicPrecision Medicine and Targeted Therapies in Gastrointestinal and Genitourinary Solid TumorsView all 21 articles

Predictive value of peripheral blood CD4⁺ T and NK cells on efficacy and long-term survival in advanced HCC patients receiving immunotherapy

Provisionally accepted
  • 1China-Japan Union Hospital of Jilin University, Changchun, China
  • 2Ezhou Central Hospital, Ezhou, China

The final, formatted version of the article will be published soon.

Background: Early assessment of the efficacy of immune checkpoint inhibitor (ICI) therapy in advanced hepatocellular carcinoma (HCC) patients plays a crucial role. In this study, we systematically analyzed the predictive values of various lymphocyte subpopulations (CD4+ T, CD8+ T, and NK cells) at different time points of pretreatment (W0), 3 weeks (W3) and 6 weeks (W6) post-treatment and their relative changes compared to W0 for objective response (OR). Materials and Methods: We systematically reviewed the clinical data of these patients in our hospital. Logistic regression analyses were conducted to identify variables predicting OR. Cut-off values were determined by maximizing Youden index. Then, patients were stratified based on these cut-off values, and Kaplan-Meier analysis with log-rank test was used to compare progression-free survival (PFS) and overall survival (OS) between groups. Results: A total of 41 patients were included. Multivariate logistic regression analysis revealed that W3 CD4+ T cells (%) and NK cells (%) were independent predictors of treatment efficacy. The odds ratios (95% confidence interval) and p-values were 1.140 (1.020-1.274), 0.021 and 2.232 (1.025-4.860), 0.043, respectively. Combining these two indicators yielded even better performance: all patients in the "All High" group achieved OR, whereas none in the "All Low" group did. Furthermore, whether used individually or in combination, they all could stratify patients by PFS and OS. Conclusions: W3 CD4+ T cells (%) and W3 NK cells (%) can predict the efficacy and long-term survival (PFS and OS) of these patients. Their combination offers improved predictive performance.

Keywords: CD4+ T cells, NK cells, hepatocellular carcinoma (HCC), Immunotherapy, treatment efficacy, Overall survival (OS), progression-free survival (PFS)

Received: 10 Aug 2025; Accepted: 17 Nov 2025.

Copyright: © 2025 Pan, Song, An, Lianyue, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Wei Li, weili888@jlu.edu.cn

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