Evidence map›Paper›PMID 42527662›Full record

ArticleCellular & molecular immunology2026

Tumor cell-released autophagosome (TRAP) programs inflammatory CAFs to drive the immune-excluded TIME through C3a.

Xuru Wang, Yiting Wei, Chengdong Wu, Xiaohe Zhou, Xiaotong Sun, Xiaoyue Du, Jinpeng Chen, Jing Chen, Wenqi Zhang, Xiangwei Bo and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular & molecular immunology, 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.

Xuru Wang *Department of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Yiting Wei *Department of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Chengdong Wu *Department of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Xiaohe Zhou *Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Xiaotong SunDepartment of Laboratory Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Xiaoyue DuDepartment of Oncology, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
Jinpeng ChenDepartment of General Surgery, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
Jing ChenDepartment of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Wenqi ZhangDepartment of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Xiangwei BoDepartment of Health Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Yunpeng ZhangDepartment of Orthopedics, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Bo ShenDepartment of Oncology, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
Shaodi WenDepartment of Oncology, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China. wenshaodi@njmu.edu.cn.
Lixin WangDepartment of Microbiology and Immunology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China. lxwang@seu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The immune-excluded tumor immune microenvironment (TIME) limits responses to ICIs. Cancer-associated fibroblasts are the most abundant stromal population and key regulators of immune suppression; however, the upstream cues that program pathogenic CAF states and the mechanisms of the immune-excluded TIME remain poorly defined. Here, by combining single-cell RNA sequencing and functional validation, we report that tumor cell-released autophagosome (TRAP) programs inflammatory CAFs (iCAFs) and triggers cathepsin L-dependent intracellular cleavage of C3 into C3a via the HSP70-TLR4-MyD88-ERK/p38 pathway. iCAF-derived C3a affects C3a on TAMs, promotes TAM accumulation in the iCAF-rich stroma, limits TIL trafficking into tumor nests, and reinforces an immune-excluded TIME. Disrupting the TRAP-iCAF-C3a/C3aR axis remodels the immune-excluded TIME and sensitizes tumors to anti-PD-L1 therapy. In clinical cohorts, plasma TRAP and C3a levels increased with disease stage, and their combination improved the discrimination of patients with breast cancer from controls (AUC = 0.96). These data define a TRAP-driven stromal-immune circuit that promotes immune exclusion and suggest that the C3a-C3aR axis is a potential target for enhancing ICI efficacy.

Indexed as

AutophagosomesCancer-Associated FibroblastsComplement C3aInflammationAnimalsCell Line, TumorFemaleHumansMiceTumor MicroenvironmentComplement C3aC3aCTSLImmune-excluded tumor immune microenvironment (TIME)Inflammatory CAFsTumor cell-released autophagosome (TRAP)

Identifiers

PMID42527662
PMCPMC13527093

What OpenQuestion holds

Textmetadata
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.