Evidence map›Paper›PMID 40510363›Full record

ArticleFrontiers in immunology2025

Harnessing NKG2D CAR-T cells with radiotherapy: a novel approach for esophageal squamous cell carcinoma treatment.

Tianyu Liu, Liyuan Fan, Weicheng Huang, Pengxiang Chen, Yuchen Liu, Shuyun Wang, Kaiyue Guo, Yufeng Cheng, Yali Han

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Tianyu Liu *Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Liyuan Fan *Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Weicheng HuangDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Pengxiang ChenDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Yuchen LiuDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Shuyun WangPhase I Clinical Trail Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Kaiyue GuoDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Yufeng ChengDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Yali HanDepartment of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) represents a highly aggressive malignancy with poor prognosis and limited therapeutic advancements. While chimeric antigen receptor (CAR)-T-cell therapy has revolutionized cancer treatment, its application in ESCC remains poorly explored. This study pioneers the exploration of natural killer group 2 member D (NKG2D) CAR-T cells combined with radiotherapy for treating ESCC, with the goals of establishing a novel treatment strategy and achieving superior tumor control through combined immunoradiotherapy. Methods: Flow cytometry and quantitative real-time PCR (qRT-PCR) were carried out to evaluate the expression of NKG2D ligands at the cell surface protein and mRNA levels. Cell-based bioluminescence assays and enzyme-linked immunosorbent assays (ELISAs) were performed to measure the cytotoxicity and cytokine secretion of NKG2D CAR-T cells. A human ESCC subcutaneous xenograft model and a bilateral xenograft model were established. Luminex liquid suspension chip detection was utilized to verify the changes in cytokines and chemokines in the circulation and at tumor sites. Immunohistochemical analysis was conducted to assess the accumulation of T cells Results: NKG2D ligands are widely expressed in ESCC cell lines and can be further increased by irradiation at both the mRNA and cell surface protein levels. NKG2D CAR-T cells efficiently recognized and lysed ESCC cell lines, and irradiation enhanced the activity of NKG2D CAR-T cells targeting ESCC cells. Additionally, NKG2D CAR-T cells specifically homed to and accumulated in ESCC tumors, exerting efficient immunological activity correlated with noticeable tumor regression in a human ESCC xenograft model, with no obvious toxicity. Moreover, preconditioning with local radiotherapy accelerated the tumor shrinkage induced by NKG2D CAR-T cells, explaining by altering the tumor microenvironment (TME) and promoting the migration and infiltration of CAR-T cells into tumor sites. Conclusions: We first clarified the therapeutic efficacy of NKG2D CAR-T cells in ESCC, as well as their enhanced effect when combined with radiotherapy, which provides a novel treatment strategy for ESCC patients.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaImmunotherapy, AdoptiveNK Cell Lectin-Like Receptor Subfamily KReceptors, Chimeric AntigenT-LymphocytesAnimalsCell Line, TumorCombined Modality TherapyCytokinesFemaleHumansMiceTumor MicroenvironmentXenograft Model Antitumor AssaysCytokinesKLRK1 protein, humanNK Cell Lectin-Like Receptor Subfamily KReceptors, Chimeric AntigenCAR-T cellscombination treatmentESCCNKG2Dradiotherapy

Identifiers

PMID40510363
PMCPMC12158975

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.