Researchers at Pitt have demonstrated that intragenic rearrangement (IGR) burden complements tumor mutation burden (TMB) in estimating neoantigen burden and possesses predictive value to anti-PDL1 treatment in TMB-low tumor entities and platinum-treated tumors.
Description
While immune checkpoint inhibitors (ICIs), which target the binding between programmed death 1 and its ligand (PD1/PD-L1), increase the survival of cancer patients, only a small subset of them receive benefits. TMB to some degree discriminates responders, whereas some patients with low TMB show outstanding responses. Thus revealing new genetic aberrations contributing to neoantigen burden will be critical to identify ICI responders. Through Pan-Cancer Analysis of Whole Genomes, it has been found that IGR burden is a pivotal contributor to increased T-inflamed signature in selected tumor entities such as breast cancer, ovarian cancer, uterine corpus endometrial cancer, and esophageal adenocarcinoma, and correlates with increased type-I immune response effectors, such as Macrophage M1 and CD8+ T cells. It has been demonstrated that IGR burden complements TMB in estimating neoantigen burden and possesses predictive value to anti-PDL1 treatment in TMB-low tumor entities and platinum-treated tumors.
Applications
• Cancer treatment response
• ICI responders
Advantages
Previous studies have demonstrated that several biomarkers are associated with ICI effectiveness, such as TMB, copy number alternation, frameshift indels, PD-L1 expression, and microsatellite instability. However, none of these is singly sufficient to discriminate all responders from non-responders, especially in TMB low cancer types. IGR burden correlates with increased T-inflamed signature in breast, ovarian, endometrial and esophageal cancers for which TMB do not have significant predictive values.
Invention Readiness
This technology is at the prototype level.
IP Status
Patent pending
