Evidence map›Paper›PMID 33934440›Full record

ArticleCancer science2021

5-Aminolevulinic acid/sodium ferrous citrate enhanced the antitumor effects of programmed cell death-ligand 1 blockade by regulation of exhausted T cell metabolism in a melanoma model.

Xin Hu, Weitao Que, Hiroshi Hirano, Zhidan Wang, Naoko Nozawa, Takuya Ishii, Masahiro Ishizuka, Hidenori Ito, Kiwamu Takahashi, Motowo Nakajima and 4 more

Abstract read
In one paragraph

Article in Cancer science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Roles of mitophagy and immune infiltration in Parkinson's disease: new perspectives from bioinformatics analysis and A53T transgenic mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  2. The Role of Mitochondrial Complexes in Liver Diseases.Journal of clinical and translational hepatology · 2025
    Review
  3. Article
  4. Article
  5. Mitochondrial Metabolism in T-Cell Exhaustion.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. Succinyl-CoA-based energy metabolism dysfunction in chronic heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Review
  11. Article
  12. Article
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.

Xin HuDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Weitao QueDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Hiroshi HiranoDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Zhidan WangDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Naoko NozawaSBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
Takuya IshiiSBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
Masahiro IshizukaSBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
Hidenori ItoSBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
Kiwamu TakahashiSBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
Motowo NakajimaSBI Pharmaceuticals Co., Ltd., Tokyo, Japan.
Tohru TanakaNeopharma Japan Co., Ltd., Tokyo, Japan.
Ping ZhuGuangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Wen-Zhi GuoDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xiao-Kang LiDivision of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.ORCID https://orcid.org/0000-0002-0897-2141

Funding

Grants of Ministry of Education, Culture, Sports, Science and Technology of Japan 16K11064Grants of Ministry of Education, Culture, Sports, Science and Technology of Japan 18K08558Grants of Ministry of Education, Culture, Sports, Science and Technology of Japan 24/17H04277National Science Foundation of China (NSFC) Projects of International Cooperation and Exchanges 81720108004
6 · The paper itself

Abstract

Mitochondria are key cytoplasmic organelles. Their activation is critical for the generation of T cell proliferation and cytotoxicity. Exhausted tumor-infiltrating T cells show a decreased mitochondrial function and mass. 5-Aminolevulinic acid (5-ALA), a natural amino acid that is only produced in the mitochondria, has been shown to influence metabolic functions. We hypothesized that 5-ALA with sodium ferrous citrate (SFC) might provide metabolic support for tumor-infiltrating T cells. In a mouse melanoma model, we found that 5-ALA/SFC with a programmed cell death-ligand 1 (PD-L1) blocking Ab synergized tumor regression. After treatment with 5-ALA/SFC and anti-PD-L1 Ab, tumor infiltrating lymphocytes (TILs) were not only competent for the production of cytolytic particles and cytokines (granzyme B, interleukin-2, and γ-interferon) but also showed enhanced Ki-67 activity (a proliferation marker). The number of activated T cells (PD-1

Indexed as

Adenosine TriphosphateAminolevulinic AcidAnimalsB7-H1 AntigenCell Line, TumorCitric AcidCombined Modality TherapyFemaleFerrous CompoundsHeme Oxygenase-1Hepatitis A Virus Cellular Receptor 2Ki-67 AntigenLymphocyte ActivationLymphocyte CountLymphocytes, Tumor-InfiltratingMelanoma, ExperimentalAdenosine TriphosphateAminolevulinic AcidB7-H1 AntigenCitric Acidferrous citrateFerrous CompoundsHAVCR2 protein, humanHeme Oxygenase-1Hepatitis A Virus Cellular Receptor 2Hmox1 protein, mouseKi-67 AntigenMembrane ProteinsNrf1 protein, mouseNuclear Respiratory Factor 1Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mouseSirt1 protein, mouseSirtuin 1cancer immunotherapyexhausted T cellmitochondrial functionPD-1/PD-L1 blockadetumor infiltrating lymphocyte

Identifiers

PMID33934440
PMCPMC8253271

What OpenQuestion holds

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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.