Evidence map›Paper›PMID 42342407›Full record

ArticleJournal for immunotherapy of cancer2026

Targeting non-canonical antigens unlocks functional T-cell responses in renal cell carcinoma.

Jiahao Wang, Yihao Zhu, Xinyu He, Shenyi Yin, Yang He, Pengju Yao, Juan Li, Xuwen Li, Peiting Shi, Renzhi Qian and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Jiahao WangState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Yihao ZhuDepartment of Urology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xinyu HeState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Shenyi YinState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Yang HeState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Pengju YaoInnovative Vaccine and Immunotherapy Research Center, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Juan LiState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Xuwen LiDepartment of Urology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Peiting ShiState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Renzhi QianState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Zhiqing XiaoState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.
Xiongjun YeDepartment of Urology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China jzxi@pku.edu.cn bqye@pku.edu.cn yexiongjun@cicams.ac.cn.
Jianzhong Jeff XiState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China jzxi@pku.edu.cn bqye@pku.edu.cn yexiongjun@cicams.ac.cn.ORCID http://orcid.org/0009-0004-6090-2636
Buqing YeState Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Tumor Organoid and Digital Tumor Twin, Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China jzxi@pku.edu.cn bqye@pku.edu.cn yexiongjun@cicams.ac.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRenal cell carcinoma (RCC) frequently exhibits favorable responses to immunotherapy, despite a low tumor mutational burden, suggesting a critical role for non-mutational antigens presented by human leukocyte antigen class I in activating CD8

methodsTo systematically identify non-canonical tumor-specific antigens, we developed an integrated proteogenomic approach to RCC samples by combining immunopeptidomics with exome and transcriptome sequencing. We subsequently primed and expanded antigen-reactive T cells in vitro, isolated a panel of antigen-specific T-cell receptors, and characterized their functionality. Finally, we investigated the tumor-killing and regression of non-canonical antigen-reactive T cells using patient-derived tumor-like cell clusters and mouse models.

resultsWe discovered a diverse repertoire of non-canonical tumor-specific antigens derived from human endogenous retroviruses (hERVs) and long non-coding RNAs (lncRNAs), many of which were shared across patients. Single-cell RNA sequencing further revealed that T cells reactive to these antigens were enriched within exhausted subsets in the tumor microenvironment, indicative of persistent antigen-specific stimulation. Functionally, T cells engineered to recognize these non-canonical antigens mediated potent tumor cell killing both in vitro and in vivo. Our findings establish hERV-derived and lncRNA-derived antigens as key drivers of RCC immunogenicity and highlight their strong potential as targets for T-cell-based immunotherapy.

conclusionsOur work is the first to demonstrate that non-canonical antigens drive immunogenicity in low-mutation RCC, thereby resolving a key question in cancer immunology-how tumors with low mutational burden can provoke robust T-cell responses.

Indexed as

Antigens, NeoplasmCarcinoma, Renal CellCD8-Positive T-LymphocytesKidney NeoplasmsT-LymphocytesAnimalsHumansImmunotherapyMiceAntigens, NeoplasmHuman leukocyte antigen - HLAImmunotherapyKidney Cancer

Identifiers

PMID42342407
PMCPMC13295777

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.