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Cells
Special Issues
Tumor Immune Responsiveness in the Era of T Cell Immunotherapy
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Tumor Immune Responsiveness in the Era of T Cell Immunotherapy

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 15 August 2026 | Viewed by 4401

Editors

Dr. Xin Li

E-Mail Website
Guest Editor
Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA
Interests: biomedical; microbiology; immunology; inflammation; antioxidant; immune metabolism
Special Issues, Collections and Topics in MDPI journals
Dr. Wenjian Wang

E-Mail Website
Guest Editor
Department of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA, USA
Interests: T cell therapy; cytokine; cancer immunology

Special Issue Information

Dear Colleagues,

Understanding the mechanisms that govern cancer immune responsiveness remains a central challenge in tumor immunology and a critical determinant of therapeutic success. Among the key players, T cells—particularly cytotoxic and helper subsets—are pivotal mediators of anti-tumor immunity. However, many tumors remain unresponsive to current therapies or develop resistance through mechanisms that impair T cell infiltration, function, or persistence.

This Special Issue will highlight cutting-edge research that expands our knowledge of how tumors interact with, evade, or are eliminated by the immune system, with a special emphasis on T cell biology and cytokine-driven modulation. We welcome original research articles and reviews that explore diverse aspects of immune responsiveness, including tumor-intrinsic and microenvironmental factors, T cell differentiation and exhaustion, cytokine signaling pathways, metabolic and epigenetic regulation, and advances in immune cell engineering.

Submissions addressing resistance to T cell–based immunotherapies, biomarkers of responsiveness, or strategies to convert immunologically “cold” tumors into T cell-infiltrated, treatment-responsive environments are particularly encouraged.

Dr. Xin Li
Dr. Wenjian Wang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • T cell-mediated immunity
  • cancer immune responsiveness
  • cytokine modulation

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Published Papers (2 papers)

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Research

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23 pages, 7014 KB  
Article
Empowerment of CAR-T Cells by IL-7 and IL-15 Boosts Their Efficacy Against HER2-Positive Tumors with Enhanced Expansion and Persistence
by Zhehong Cheng, Henning Kirchgessner, Beate Jahraus, Emre Balta and Yvonne Samstag
Cells 2026, 15(6), 547; https://doi.org/10.3390/cells15060547 - 19 Mar 2026
Cited by 1 | Viewed by 1976
Abstract
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable clinical success in B cell malignancies. However, its efficacy in solid tumors remains limited, in part due to suboptimal expansion, persistence, and restrained effector function. Strategies that promote durable CAR-T cell fitness are therefore [...] Read more.
Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable clinical success in B cell malignancies. However, its efficacy in solid tumors remains limited, in part due to suboptimal expansion, persistence, and restrained effector function. Strategies that promote durable CAR-T cell fitness are therefore required to overcome these barriers. In this study, we generated HER2-CAR-T cells targeting human breast cancer cells and evaluated the impact of different cytokine supplementation strategies on CAR-T cell phenotype and function. We analyzed gene expression patterns and performed repetitive tumor killing assays to assess the ability of CAR-T cells expanded with IL-2 + IL-7 + IL-15 compared with IL-2 alone to maintain proliferation and cytotoxic function across multiple rounds of tumor cell exposure. Compared with IL-2 alone, supplementation with IL-7 and IL-15 significantly enhanced CAR-T cell expansion, preserved stem cell-like features prior to antigen encounter, and promoted superior proliferative capacity. Moreover, CAR-T cells cultured with IL-7+15 or IL-2+7+15 maintained sustained cytotoxicity and exhibited increased antitumor cytokine production during repeated tumor challenges. Notably, IL-7 and IL-15 supplementation induced a CD57+ CAR-T cell population that, unlike the immunosenescent CD57+ cells reported previously, retained full proliferative and cytotoxic capacity, with CD57 expression being dynamically downregulated upon antigen stimulation. Collectively, these findings demonstrate that incorporation of IL-7 and IL-15 into CAR-T cell manufacturing protocols substantially improves expansion, persistence, and effector function, supporting their use as a strategy to enhance CAR-T cell performance against solid tumors. Full article
(This article belongs to the Special Issue Tumor Immune Responsiveness in the Era of T Cell Immunotherapy)
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Review

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32 pages, 2119 KB  
Review
The Role of CD4+ T Helper Cell Subsets in Hepatocellular Carcinoma: Implications for Tumour Progression and Immunotherapy
by Jijie Shao, Jintong Na, Honghua Huang, Lei Xiao, Fengqiu Dang, Rongshun Zheng, Liping Zhong and Yongxiang Zhao
Cells 2026, 15(4), 350; https://doi.org/10.3390/cells15040350 - 15 Feb 2026
Cited by 1 | Viewed by 1756
Abstract
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality; its progression is strongly linked to the liver’s immune microenvironment. T-helper (Th) cells, including Th1, Th2, Th17, and regulatory T cells (Tregs), play pivotal roles in modulating tumour immunity, either promoting [...] Read more.
Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality; its progression is strongly linked to the liver’s immune microenvironment. T-helper (Th) cells, including Th1, Th2, Th17, and regulatory T cells (Tregs), play pivotal roles in modulating tumour immunity, either promoting or inhibiting tumour growth depending on their functional states and interactions within the tumour microenvironment. Imbalances in Th cell subsets, particularly between pro-inflammatory and immunosuppressive populations, have been associated with HCC progression and poor prognosis. Numerous studies have explored the therapeutic potential of restoring balance among Th cell subsets, focusing on modulating immune responses to improve HCC treatment outcomes. This paper reviews the differentiation and functional roles of Th cell subsets in HCC, exploring their contributions to tumour progression and immune suppression. Furthermore, this study discusses emerging immunotherapies aimed at modulating Th cell populations to improve clinical outcomes for HCC patients. Understanding the intricate roles of Th cells in the tumour microenvironment provides valuable insights for developing novel therapeutic strategies for liver cancer. Full article
(This article belongs to the Special Issue Tumor Immune Responsiveness in the Era of T Cell Immunotherapy)
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