Evidence map›Paper›PMID 40368902›Full record

ArticleCell death & disease2025

Chemotherapy-induced macrophage CXCL7 expression drives tumor chemoresistance via the STAT1/PHGDH-serine metabolism axis and SAM paracrine feedback to M2 polarization.

Shuguang Liu, Hui Gong, Peihang Li, Jiahao Hu, Yixuan Li, Rou Xu, Junchao Cai, Shuqi Wang, Jiayi Cai, Hongmei Ma and 8 more

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Harnessing chimeric antigen receptor macrophages against solid tumors.Cancer communications (London, England) · 2025
    Review
  10. 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

18 authors.

Shuguang Liu *Department of pathology, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China.
Hui Gong *Shenzhen Nanshan People's Hospital, Shenzhen, China.ORCID http://orcid.org/0000-0003-3707-8429
Peihang Li *Medical Research Center, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China.ORCID http://orcid.org/0009-0008-4698-921X
Jiahao Hu *Medical Research Center, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China.ORCID http://orcid.org/0009-0009-0361-9486
Yixuan LiMedical Research Center, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China.
Rou XuMedical Research Center, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China.
Junchao CaiDepartment of Immunology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Shuqi WangDepartment of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Jiayi CaiDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Hongmei MaDepartment of pathology, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China.
Xirong MiShenzhen University Medical School, Shenzhen, Guangdong, China.
Yifan LiShenzhen Nanshan People's Hospital, Shenzhen, China.ORCID http://orcid.org/0000-0002-3895-1974
Qingbo ZhouDepartment of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Qiming ZhouShenzhen Nanshan People's Hospital, Shenzhen, China. zqm19771221@163.com.ORCID http://orcid.org/0000-0002-6539-8043
Weiqiang YangDepartment of Otolaryngology, Peking University Shenzhen Hospital, Shenzhen, China. 497450210@qq.com.ORCID http://orcid.org/0000-0002-2511-7948
Riqing LiShenzhen Inspection and Testing Center of Agricultural Product Quality and Safety, Shenzhen, China. liriqing246@163.com.ORCID http://orcid.org/0000-0003-4397-2056
Libing SongDepartment of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China. songlb@sysucc.org.cn.ORCID http://orcid.org/0000-0002-5315-771X
Lishan FangMedical Research Center, The Eighth Affiliated Hospital, Sun Yat-Sun University, Shenzhen, China. fanglsh5@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-0183-861X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82372913, 8220367
6 · The paper itself

Abstract

Chemotherapy resistance in colorectal cancer (CRC) remains a major obstacle in clinical oncology. Analysis of clinical specimens from chemotherapy-resistant patients revealed elevated CXCL7 expression in tumor-associated macrophages (TAMs). Through integrated in vitro and in vivo studies, we demonstrated that chemotherapy induces tumor cell-macrophage crosstalk, leading to CXCL7 upregulation in TAMs. Using a co-culture system, we observed that CXCL7+ macrophages confer chemoresistance to CRC cells. Mechanistic investigations revealed that CXCL7 activates the CXCR2 receptor on tumor cells, triggering interferon signaling and promoting serine metabolism through STAT1-dependent transcriptional upregulation of phosphoglycerate dehydrogenase (PHGDH), the key enzyme in serine biosynthesis. This metabolic reprogramming enhances the paracrine secretion of S-adenosyl methionine (SAM), which drives chemotherapy resistance. Furthermore, CXCL7-mediated the paracrine secretion of SAM in tumor cells, which in turn promotes M2 macrophage polarization and sustains CXCL7 expression in TAMs. Our findings reveal that a CXCL7-SAM feedback loop between tumor cells and macrophages establishes a chemoresistant niche. This interaction represents a promising therapeutic target for overcoming chemoresistance in CRC.

Indexed as

Colorectal NeoplasmsDrug Resistance, NeoplasmMacrophagesParacrine CommunicationPhosphoglycerate DehydrogenaseS-AdenosylmethionineSerineSTAT1 Transcription FactorAnimalsCell Line, TumorFeedback, PhysiologicalGene Expression Regulation, NeoplasticHumansMiceTumor-Associated MacrophagesPhosphoglycerate DehydrogenaseS-AdenosylmethionineSerineSTAT1 protein, humanSTAT1 Transcription Factor

Identifiers

PMID40368902
PMCPMC12078479

What Socratic holds

Textmetadata
LicenceCC BY
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.