Is VISTA:VSIG3 an Actionable Immune Checkpoint Target in Kidney Cancer?
Abstract
Background: For cancers to grow, they must evade destruction by the immune system. Many cancers evade the immune system by expressing molecules that turn off the anti-cancer immune response. Blocking these inhibitory checkpoints, like Programmed cell death-1 (PD-1), has become a standard therapy for treatment of many types of tumors including kidney cancer. Combining immune checkpoint inhibitors has been shown to improve outcomes for patients with kidney cancer. However, many patients fail to respond to currently available immune checkpoint inhibitors. These tumors appear to have a smoldering antitumor immune response that is turned off by expression of other negative immune regulators related to PD-1, such as VISTA. VISTA is an immune checkpoint that is highly expressed across kidney cancers, and a subset of kidney tumors also expresses VISTA s binding partners: VSIG3 and VSIG8. Objectives: My primary goal is to determine if targeting receptors of the VISTA pathway, VSIG3 or VSIG8, can overcome PD-1 resistance in a mouse kidney cancer model. This proposal addresses multiple KCRP Areas of Emphasis, including immunotherapies and resistance to standard therapy. Innovation: By determining if blocking the function of VSIG3 and VSIG8 overcomes the tumor s ability to evade the immune system in a mouse model, we may be able to develop better therapeutics for blocking this pathway in patients with cancer. Impact: In addition to investigating VISTA:VSIG3 or VSIG8 as a target for fighting cancer, we will study patients tumors to explore biomarkers that would predict whether the therapy is likely to work. This could help to determine which patients will most likely benefit from VISTA pathway inhibitors and facilitate the development of new therapies to treat patients with kidney cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810500
Entities
People
- Kathleen M Mahoney
Organizations
- Dana–Farber Cancer Institute
- United States Army