Related Experiment Video

Updated: Oct 28, 2025

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

7.0K

Targeting Axl favors an antitumorigenic microenvironment that enhances immunotherapy responses by decreasing Hif-1α

Marie-Anne Goyette1,2, Islam E Elkholi1,2, Chloé Apcher1,2

  • 1Cytoskeletal Organization and Cell Migration, Montreal Clinical Research Institute, Montréal, QC H2W 1R7, Canada.

Proceedings of the National Academy of Sciences of the United States of America
|July 16, 2021
PubMed

Insights

Targeting AXL in HER2+ breast cancer dampens hypoxia, normalizes tumor blood vessels, and reduces metastasis. Combining AXL inhibition with anti-PD-1 immunotherapy shows promise for treating hypoxic tumors.

Area of Science:

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background:

  • Hypoxia is a key driver of tumor progression, metastasis, and therapy resistance.
  • The receptor tyrosine kinase AXL is implicated in tumor biology, but its role in hypoxia-induced tumor microenvironment (TME) deregulation is unclear.

Purpose of the Study:

  • To investigate the role of AXL in hypoxia-driven TME deregulation and metastasis in HER2+ breast cancer.
  • To evaluate the therapeutic potential of AXL inhibition, alone and in combination with anti-PD-1 immunotherapy.

Main Methods:

  • Mammary gland-specific deletion of AXL in a HER2+ mouse model.
  • Assessment of tumor vasculature, TME, and metastatic burden.
  • Pharmacological inhibition of AXL combined with anti-PD-1 therapy.

Main Results:

  • AXL deletion normalized tumor vasculature and induced a proinflammatory TME.
  • Interfering with AXL reduced hypoxia-induced HIF-1α levels, epithelial-to-mesenchymal transition (EMT), and invasion.
  • Combined AXL inhibition and anti-PD-1 therapy reduced primary tumor and metastatic burdens.

Conclusions:

  • AXL inhibition mitigates hypoxia-driven tumor progression and metastasis in HER2+ breast cancer.
  • Targeting AXL creates a favorable environment for immunotherapy, offering a potential therapeutic strategy for hypoxic HER2+ tumors.
Keywords:
AXLHER2hypoxiaimmunotherapytumor microenvironment

More Related Videos

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

3.7K
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.1K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
780
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.1K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.3K