Evidence map›Paper›PMID 30934955›Full record

ArticleCancers2019

Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma.

Saeed Daneshmandi, Barbara Wegiel, Pankaj Seth

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 1 pooled it
6.8field-weighted citation impact, top 2% of its field
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

110 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Lactylation Modification and Esophageal Cancer: Research Progress From Hypoxia-Induced Metabolic Reprogramming to Immune Escape.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Lactate, a Spearhead of Cancer Aggressiveness: Metabolic Reprogramming, Immune Suppression, and Metastatic Progression.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026
    Review
  20. Review

50 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Saeed DaneshmandiDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. sdaneshm@bidmc.harvard.edu.
Barbara WegielDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. bwegiel@bidmc.harvard.edu.
Pankaj SethDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. bwegiel@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · US

Funding

Heme degradation pathway and immunomodulation in prostate cancer.R21CA169904 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WEGIEL, BARBARA · 2013 to 2014
$411k
NCI NIH HHS R21 CA169904
6 · The paper itself

Abstract

Immunotherapy is a curable treatment for certain cancers, but it is still only effective in a small subset of patients. We have recently reported that programmed cell death protein-1 (PD-1) ligand (PD-L1) expression is regulated by lactate present at high levels in the tumor microenvironment (TME). We hypothesized that the efficacy of anti-PD-1 treatment can be improved by blocking the lactate-generating enzyme, lactate dehydrogenase-A (LDH-A). Anti-PD-1 treatment of mice harboring LDH-A deficient B16-F10 melanoma tumors led to an increase in anti-tumor immune responses compared to mice implanted with tumors expressing LDH-A. Specifically, we observed heightened infiltration of natural killer (NK) cells and CD8⁺ cytotoxic T cells in the LDH-A deficient tumors. These infiltrated cytotoxic cells had an elevated production of interferon-γ (IFN-γ) and granzyme B. Mechanistically, CD8⁺ T cells isolated from the TME of LDH-A deficient B16-F10 melanoma tumors and treated with anti-PD-1 showed enhanced mitochondrial activity and increased reactive oxygen species (ROS) levels. Moreover, infiltration of T regulatory (Treg) cells was diminished in LDH-A deficient tumors treated with anti-PD-1. These altered immune cell profiles were clinically relevant as they were accompanied by significantly reduced tumor growth. Our study suggests that blocking LDH-A in the tumor might improve the efficacy of anti-PD-1 therapy.

Indexed as

lactateLDH-AmelanomaPD-1PD-L1

Identifiers

PMID30934955
PMCPMC6521327
OpenAlexW2922700235

What OpenQuestion 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 OpenQuestion graph.