Evidence map›Paper›PMID 39631851›Full record

ArticleJournal for immunotherapy of cancer2024

Mitochondrial metabolic reprogramming of macrophages and T cells enhances CD47 antibody-engineered oncolytic virus antitumor immunity.

Jing Zhao, Shichuan Hu, Zhongbing Qi, Xianglin Xu, Xiangyu Long, Anliang Huang, Jiyan Liu, Ping Cheng

Abstract 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. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Article
  3. Article
  4. Review
  5. Progress in Designing Cytokine Antagonist Antibodies for Cancer Therapy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025
    Review
  10. Review
  11. 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

8 authors.

Jing Zhao *Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Shichuan Hu *Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Zhongbing Qi *Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Xianglin Xu *Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Xiangyu LongDepartment of Oncology, Guangan People's Hospital, Sichuan, Guangan, China.
Anliang HuangDepartment of Pathology, Chengdu Fifth People's Hospital, Chengdu, China.
Jiyan LiuDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China liujiyan1972@163.com ping.cheng@foxmail.com.
Ping ChengDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China liujiyan1972@163.com ping.cheng@foxmail.com.ORCID 0000-0001-5440-5941

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlthough immunotherapy can reinvigorate immune cells to clear tumors, the response rates are poor in some patients. Here, CD47 antibody-engineered oncolytic viruses (oAd-αCD47) were employed to lyse tumors and activate immunity. The oAd-αCD47 induced comprehensive remodeling of the tumor microenvironment (TME). However, whether the acidic TME affects the antitumor immunotherapeutic effects of oncolytic viruses-αCD47 has not been clarified.

methodsTo assess the impact of oAd-αCD47 treatment on the TME, we employed multicolor flow cytometry. Glucose uptake was quantified using 2NBDG, while mitochondrial content was evaluated with MitoTracker FM dye. pH imaging of tumors was performed using the pH-sensitive fluorophore SNARF-4F. Moreover, changes in the calmodulin-dependent protein kinase II (CaMKII)/cyclic AMP activates-responsive element-binding proteins (CREB) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) signaling pathway were confirmed through western blotting and flow cytometry.

resultsHere, we identified sodium bicarbonate (NaBi) as the potent metabolic reprogramming agent that enhanced antitumor responses in the acidic TME. The combination of NaBi and oAd-αCD47 therapy significantly inhibited tumor growth and produced complete immune control in various tumor-bearing mouse models. Mechanistically, combination therapy mainly reduced the number of regulatory T cells and enriched the ratio of M1-type macrophages TAMs (M1.TAMs) to M2-type macrophages TAMs (M2.TAMs), while decreasing the abundance of PD-1

conclusionsTumor acidic microenvironment impairs mitochondrial energy metabolism in macrophages and T cells inducing oAd-αCD47 immunotherapeutic resistance. NaBi improves the acidity of the TME and activates the CaMKII/CREB/PGC1α mitochondrial biosynthesis signaling pathway, which reprograms the energy metabolism of macrophages and T cells in the TME, and oral NaBi enhances the antitumor effect of oAd-αCD47.

Indexed as

CD47 AntigenMacrophagesMitochondriaOncolytic VirusesTumor MicroenvironmentAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell Line, TumorCellular ReprogrammingCyclic AMP Response Element-Binding ProteinFemaleHumansMetabolic ReprogrammingMiceNeoplasmsOncolytic VirotherapyCalcium-Calmodulin-Dependent Protein Kinase Type 2CD47 AntigenCyclic AMP Response Element-Binding ProteinPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseCombination therapyImmunosuppressionImmunotherapyOncolytic virus

Identifiers

PMID39631851
PMCPMC11624815

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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.