Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 212, Issue 2, Pages 139-148Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20140559
Keywords
-
Categories
Funding
- Roche
- Pfizer
- Association pour la Recherche contre le Cancer
- Ligue contre le Cancer
- Association des Gastroenterologues Oncologues
- Association Benoit Malassagne
- Societe Francaise de Chirurgie Digestive
- Assistance Publique - Hopitaux de Paris (APHP - FERCM)
- Site de Recherche Integre sur le Cancer-Programme Cancer Research for Personalized Medicine (CARPEM)
- Labex Immunooncology
- Grants-in-Aid for Scientific Research [26290059] Funding Source: KAKEN
Ask authors/readers for more resources
Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and a progressive loss of function. The recent development of therapies targeting PD-1 and CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key role in the development of an immunosuppressive microenvironment. We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8(+) T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A-VEGFR. In view of these results, association of anti-angiogenic molecules with immunomodulators of inhibitory checkpoints may be of particular interest in VEGF-A-producing tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available