Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
Cancer Therapies02:49

Cancer Therapies

7.7K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.7K
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Oncology And Carcinogenesis
  9. Predictive And Prognostic Markers
  11. Wtap-induced N6-methyladenosine Of Pd-l1 Blocked T-cell-mediated Antitumor Activity Under Hypoxia In Colorectal Cancer.

WTAP-induced N6-methyladenosine of PD-L1 blocked T-cell-mediated antitumor activity under hypoxia in colorectal cancer.

Qi-Zhi Liu1, Nan Zhang1, Jun-Yi Chen1

  • 1Department of Gastrointestinal Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Cancer Science
|March 20, 2024

Related Experiment Videos

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

308
Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue
10:11

Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue

Published on: January 3, 2013

23.1K
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
06:07

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

Published on: February 5, 2020

5.7K

View abstract on PubMed

Summary
This summary is machine-generated.

Wilms' tumor 1-associated protein (WTAP) regulates PD-L1 expression epigenetically, impacting colorectal cancer (CRC) immune evasion. Targeting WTAP shows promise for hypoxia-driven tumor immunotherapy.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Immunology

Background:

  • N6-Methyladenosine (m6A) modification is a key post-transcriptional regulator of gene expression.
  • Programmed death ligand 1 (PD-L1) is a critical immune checkpoint protein involved in tumor immune evasion.
  • Wilms' tumor 1-associated protein (WTAP) is implicated in m6A modification and cancer progression.

Purpose of the Study:

  • To elucidate the regulatory mechanism of PD-L1 expression by WTAP in colorectal cancer (CRC) under hypoxic conditions.
  • To investigate the role of WTAP in immune evasion and its potential as an immunotherapy target.

Main Methods:

  • Investigated WTAP degradation and its regulation by Pumilio homolog 1 (PUM1) in CRC cells under hypoxia.
  • Assessed the m6A-dependent enhancement of PD-L1 expression by WTAP.
Keywords:
PD‐L1Wilms tumor 1‐associated proteincolorectal cancerhypoxia

Related Experiment Videos

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

308
Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue
10:11

Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue

Published on: January 3, 2013

23.1K
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
06:07

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

Published on: February 5, 2020

5.7K
  • Utilized m6A 'reader' protein IGF2BP2 to identify and stabilize methylated PD-L1 mRNA.
  • Evaluated the impact of WTAP overexpression on T-cell proliferation and anti-tumor activity in vitro and in vivo.
  • Analyzed WTAP-PD-L1 axis in human CRC tissues and organoids.
  • Correlated WTAP levels with patient response to anti-PD1 immunotherapy.

    • Main Results:

    • Hypoxia-induced WTAP degradation in CRC cells is inhibited by PUM1 binding.
    • WTAP enhances PD-L1 expression in an m6A-dependent manner.
    • IGF2BP2 binds to methylated PD-L1 mRNA, stabilizing it.
    • WTAP overexpression suppresses T-cell proliferation and anti-tumor immunity by maintaining PD-L1 expression.
    • A positive correlation exists between high WTAP levels and responsiveness to anti-PD1 immunotherapy in CRC patients.

    Conclusions:

    • WTAP epigenetically regulates PD-L1 expression via m6A modification, promoting immune evasion in colorectal cancer.
    • The WTAP-PD-L1 axis represents a novel mechanism of immune suppression in hypoxic tumors.
    • Targeting WTAP offers a potential therapeutic strategy for enhancing anti-tumor immunity, particularly in the context of tumor hypoxia and anti-PD1 immunotherapy.
    immunotherapy