Evidence map›Paper›PMID 39532433›Full record

ArticleJournal for immunotherapy of cancer2024

ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis.

Lixue Cao, Haojie Peng, Yanzhen Chen, Baijin Xia, Tao Zeng, Jialing Guo, Fei Yu, Haiyan Ye, Hui Zhang, Xinxin Chen

Erratum issuedAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. CST7Translational cancer research · 2025
    Article
  7. Review
  8. Article
  9. Review
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Lixue Cao *Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.ORCID 0000-0002-0486-6587
Haojie Peng *Department of Breast Surgery, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Yanzhen Chen *Department of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Baijin Xia *Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Tao ZengDepartment of Breast Surgery, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Jialing GuoMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Fei YuMedical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China chenxinxin@gzhmu.edu.cn zhangh92@mail.sysu.edu.cn yehaiyan@gdph.org.cn yufei@gdph.org.cn.ORCID 0000-0003-1546-9365
Haiyan YeDepartment of Gynecology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China chenxinxin@gzhmu.edu.cn zhangh92@mail.sysu.edu.cn yehaiyan@gdph.org.cn yufei@gdph.org.cn.
Hui ZhangInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China chenxinxin@gzhmu.edu.cn zhangh92@mail.sysu.edu.cn yehaiyan@gdph.org.cn yufei@gdph.org.cn.ORCID 0000-0003-3620-610X
Xinxin ChenDepartment of Breast Surgery, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China chenxinxin@gzhmu.edu.cn zhangh92@mail.sysu.edu.cn yehaiyan@gdph.org.cn yufei@gdph.org.cn.ORCID 0009-0006-0846-8355

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe failure of conventional therapies and the propensity for recurrence and metastasis make triple-negative breast cancer (TNBC) a formidable challenge with grim prognoses and diminished survival rates. Immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapy, presents innovative and potentially more effective strategies for addressing TNBC. Within this context, the inducible costimulator (ICOS), a member of the CTLA4/CD28 family, plays a crucial role in regulating immune responses and T-cell differentiation by binding to its ligand ICOSL. However, the impact of the ICOS/ICOSL axis on cancer varies.

methodsIn this study, immunohistochemistry was conducted to examine the expression level of ICOSL in TNBC tumor tissues. We developed ICOS-enhanced B7H3-CAR-T cells (ICOS-B7H3-CAR) using the third-generation CAR-T cell technology, which featured magnified ICOS expression and targeted the B7H3 antigen. Xenograft and metastasis models of TNBC were conducted to examine the cytotoxicity and durability of CAR-T cells in tumors. Overexpression and CRISPR/Cas9-mediated knockout (KO) techniques were employed to regulate the expression of ICOSL on TNBC cell lines.

resultsNotably, we observed elevated ICOSL expression in TNBC tumor tissues, which correlated with poor survival prognosis in patients with TNBC. Compared with conventional B7H3-CAR-T cells, ICOS-B7H3-CAR-T cells significantly inhibited the tumor growth of TNBC cells both in vitro and in vivo, accompanied by increased secretion of cytokines such as interferon gamma and tumor necrosis factor alpha. Furthermore, the in vivo experiments illustrated that ICOS-B7H3-CAR-T cells exhibited prolonged antitumor activity and could effectively eradicate metastases in a TNBC metastasis model, consequently extending survival. Importantly, manipulating the expression of ICOSL on TNBC cells through overexpression or KO significantly influenced the function of ICOS-B7H3-CAR-T cells. This suggests that the level of ICOSL expression on TNBC cells is critical for enhancing the potent antitumor effects of ICOS-B7H3-CAR-T cells.

conclusionOverall, our study highlights the potential clinical application of ICOS as a promising strategy for combating TNBC recurrence and metastasis.

Indexed as

Immunotherapy, AdoptiveInducible T-Cell Co-Stimulator ProteinTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleHumansMiceNeoplasm MetastasisReceptors, Chimeric AntigenXenograft Model Antitumor AssaysICOS protein, humanInducible T-Cell Co-Stimulator ProteinReceptors, Chimeric AntigenImmunotherapy

Identifiers

PMID39532433
PMCPMC11555110

What Socratic 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 Socratic graph.