Evidence map›Paper›PMID 40507229›Full record

ReviewCancers2025

Regulatory Mechanisms and Therapeutic Targeting of PD-L1 Trafficking and Stability in Cancer Immunotherapy.

Muralidharan Mani, Jeong Woo Park, Thomas F J Martin

Abstract readReview
In one paragraph

Review in Cancers, 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. Review
  3. Review
  4. Review
  5. Involvement of the PD-1 pathway in the modulation of immune responses during allergic diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Frontiers in immunology · 2025
    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

3 authors.

Muralidharan ManiDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0000-0002-1194-3616
Jeong Woo ParkBasic-Clinic Convergence Research Institute, University of Ulsan, Ulsan 44610, Republic of Korea.
Thomas F J MartinDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0000-0002-5204-0202

Funding

THE MECHANISM OF ACTION OF THYROTROPIN-RELEASING HORMONER01DK025861 · NIDDK · UNIVERSITY OF WISCONSIN-MADISON · PI MARTIN, THOMAS F. J. · 1986 to 2024
$5.6M
NIDDK NIH HHS R01 DK025861NIH HHS R01DK025861
6 · The paper itself

Abstract

The PD-L1/PD-1 signaling axis is a pivotal regulator of T-cell activity and a key mechanism by which tumors evade immune surveillance. Inhibiting this pathway has resulted in significant anti-tumor responses, establishing immune checkpoint blockade (ICB) as a crucial component of modern cancer therapy. However, many patients with high PD-L1 expression do not respond to PD-1/PD-L1 blockade, underscoring the necessity for a deeper investigation into the mechanisms underlying this resistance. Recent studies have identified DRG2 as a critical modulator of anti-PD-1 therapeutic efficacy. While DRG2 depletion enhances IFN-γ signaling and increases the overall PD-L1 levels, it disrupts the recycling of endosomal PD-L1, resulting in reduced surface expression and impaired PD-1 interaction, ultimately compromising therapeutic outcomes. Furthermore, TRAPPC4, HIP1R, and CMTM6 help stabilize PD-L1 by preventing lysosome degradation. When depleted, these proteins have been shown to boost the body's immune response against tumors. Research into the complex regulatory mechanisms of PD-L1 suggests that targeting DRG2, TRAPPC4, HIP1R, and CMTM6 could enhance the effectiveness of PD-1/PD-L1 blockade therapies. This strategy could create exciting new possibilities for cancer immunotherapy and improve patient outcomes.

Indexed as

CMTM6HIP1Rimmune checkpoint blockadeimmune checkpoint blockade DRG2PD-1 pathwayPD-L1 traffickingpost-translational modificationsRas-associated binding proteins (Rab)TRAPPC4tumor immune evasion

Identifiers

PMID40507229
PMCPMC12153565

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.