Evidence map›Paper›PMID 40855305›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Functional tumor-reactive CD8 + T cells in pancreatic cancer.

Hongwei Sun, Changying Shi, Guoqing Fang, Qiufang Guo, Zhengliang Du, Geer Chen, Yasong Wu, Zhe-Sheng Chen, Jian Hua, Yan Zhang and 1 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 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. HLA-II Expression Marks Activated and Clonally Expanded CD8International journal of molecular sciences · 2026
    Article
  3. Article
  4. Review
  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

11 authors.

Hongwei Sun *Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, China.
Changying Shi *Hepatobiliary Surgery Center, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Guoqing Fang *Shanghai JFKR Organoid Biotechnology Co., Ltd, Shanghai, China.
Qiufang GuoShanghai Pharmaceutical Biotherapeutics, Cellular Therapeutics Center for Cancers, Co., Ltd, shanghai, China.
Zhengliang DuZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, China.
Geer ChenZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, China.
Yasong WuChineo Medical Technology Co. Ltd, Beijing, China.
Zhe-Sheng ChenDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, USA.
Jian HuaShanghai Pharmaceutical Biotherapeutics, Cellular Therapeutics Center for Cancers, Co., Ltd, shanghai, China. huaj@sphchina.com.
Yan ZhangZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, China. zhangyan@wmu.edu.cn.
Zhiwen ShiZhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, The First Affiliated Hospital of Wenzhou Medical University, WenZhou, China. wenzhishi@sina.com.

Funding

Natural Science Foundation of Zhejiang Province LQN25H160055the Basic scientific research Project of Wenzhou Medical University NO. KYYW202107the Key Projects Jointly Constructed by Department of Science and Technology of National Administration of Traditional Chinese Medcine & Administration of Traditional Chinese Medcine of Zhejiang Province NO.GZY-ZJ-KJ-24088Wenzhou Basic Scientific Research Project Y20240025
6 · The paper itself

Abstract

backgroundTraditional methods for detecting tumor-reactive (TR) CD8 + tumor-infiltrating lymphocytes (TILs) in pancreatic cancer usually focus on neo-antigenic epitopes, which is limited by the narrow range of antigenic epitopes, and the lengthy and complex identification processes, resulting in an incomplete understanding of the biological characteristics of TR CD8 + TILs.

methodsThis study introduces a novel approach that integrates single-cell sequencing with deep learning (DL), which enables the identification of tumor-reactive CD8 + T cells without neoantigen screening. The T Cell Receptor Engineered T (TCR-T) cell tumor organoid killing model was employed to validate the functionality of DL-identified TR CD8 + T cells, while spatial transcriptomics was used to confirm receptor-ligand interactions involving TR CD8 + TILs.

resultsComprehensive analyses of TR CD8 + TILs revealed impaired mitochondrial respiratory chain-related pathways regulated by the transcription factor FOS. The TIGIT-NECTIN2 axis was identified as an important immune checkpoint molecule in the tumor microenvironment of pancreatic cancer. T cell receptor (TCR) repertoire analysis demonstrated that some TR CD8 + TILs possess multiple TCR αβ combinations. Furthermore, TCR-T targeting experiments using tumor organoids revealed that combinations of multiple distinct TR TCRs exhibit significantly superior tumor-killing capabilities compared to a single type TCR. Clinically, a higher proportion of TR CD8 + TILs was positively associated with improved responses to neoadjuvant immunotherapy and longer overall survival in pancreatic cancer patients.

conclusionThis study represents a significant advancement in the understanding of TR TIL biology and provides a rapid and accurate method to identify TR CD8 TILs.

Indexed as

CD8-Positive T-LymphocytesLymphocytes, Tumor-InfiltratingPancreatic NeoplasmsAnimalsHumansMiceTumor MicroenvironmentDeep learningPancreatic cancerSingle cell sequencingTumor-reactive CD8 + TILs

Identifiers

PMID40855305
PMCPMC12379552

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Registered trials

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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.