Evidence map›Paper›PMID 40308191›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Lactic acid inhibits the interaction between PD-L1 protein and PD-L1 antibody in the PD-1/PD-L1 blockade therapy-resistant tumor.

Wonkyung Oh, Alyssa Min Jung Kim, Deepika Dhawan, Deborah W Knapp, Seung-Oe Lim

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–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

23 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  12. [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026
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  17. Integrating Metabolic Modulation and Nanomedicine for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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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

5 authors.

Wonkyung OhDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Alyssa Min Jung KimDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Deepika DhawanDepartment of Veterinary Clinical Science, Purdue University, West Lafayette, IN 47907, USA.
Deborah W KnappDepartment of Veterinary Clinical Science, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
Seung-Oe LimDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Cancer Research, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, USA. Electronic address: limsoe@purdue.edu.

Funding

Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI Andrea L Kasinski · 1985 to 2026
$43.4M
NCI NIH HHS P30 CA023168
6 · The paper itself

Abstract

Immune checkpoint blockade therapy targeting the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has shown remarkable clinical impact in multiple cancer types. Nonetheless, despite the recent success of PD-1/PD-L1 blockade therapy, such response rates in cancer patients have been limited to tumors encompassing specific tumor microenvironment characteristics. The altered metabolic activity of cancer cells shapes the anti-tumor immune response by affecting the activity of immune cells. However, it remains mostly unknown how the altered metabolic activity of cancer cells impacts their resistance to PD-1/PD-L1 blockade therapy. Here, we found that tumor cell-derived lactic acid renders the immunosuppressive tumor microenvironment in the PD-1/PD-L1 blockade-resistant tumors by inhibiting the interaction between the PD-L1 protein and anti-PD-L1 antibody. Furthermore, we showed that the combination therapy of targeting PD-L1 with our PD-L1 antibody-drug conjugate (PD-L1-ADC) and reducing lactic acid with the monocarboxylate transporter 1 (MCT-1) inhibitor, AZD3965, can effectively treat the PD-1/PD-L1 blockade-resistant tumors. The findings of this study provide a new mechanism of how lactic acid induces an immunosuppressive tumor microenvironment and suggest a potential combination treatment to overcome the tumor resistance to PD-1/PD-L1 blockade therapy.

Indexed as

B7-H1 AntigenDrug Resistance, NeoplasmImmune Checkpoint InhibitorsLactic AcidNeoplasmsProgrammed Cell Death 1 ReceptorAnimalsCell Line, TumorHumansMiceMonocarboxylic Acid TransportersTumor MicroenvironmentXenograft Model Antitumor AssaysB7-H1 AntigenCD274 protein, humanImmune Checkpoint InhibitorsLactic AcidMonocarboxylic Acid TransportersPDCD1 protein, humanProgrammed Cell Death 1 Receptorantibodyantibody-drug conjugateimmunotherapylactic acidPD-L1PD-l/PD-L1 blockade therapyresistancetumor microenvironment

Identifiers

PMID40308191
PMCPMC11852701

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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.