The Impact of the SETD7 gene on Outcomes in Advanced Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors

Kidney cancer, also called Renal Cell Carcinoma (RCC), affects tens of thousands of people each year worldwide and can be life-threatening. In recent years, new treatments called immune checkpoint inhibitors (ICIs) have helped many patients live longer. ICIs work by helping the body’s own immune system recognize and attack cancer cells. However, these medicines do not work for everyone. Some patients do not respond at all, and others respond at first but the cancer later grows again. Right now, doctors do not have a good way to predict which patients will benefit from ICIs.

We will study a gene called SETD7 (SET Domain Containing 7). Genes provide instructions that tell cells how to behave and SETD7 affects how certain proteins function inside cancer cells. One of the proteins influenced by SETD7 is programmed death-ligand 1 (PD-L1), a molecule that allows cancer cells to hide from the immune system. Research in other cancers suggests that SETD7 may help tumors resist ICIs. We have already obtained three RNAseq datasets (IMmotion 151, JAVELIN RENAL 101, Checkmate 025) and found that the patients with high SETD7 expression are associated with poor prognosis.

To further explore this, we will analyze data from a large international clinical trial of kidney cancer treatment called CheckMate-214. We will analyze the amount of SETD7 in each patient’s tumor and compare these levels with patient outcomes. These outcomes will include whether the tumor shrank with treatment, how long it took before the cancer worsened, and how long patients lived overall.

We will also compare results between patients who received ICIs and those who received the standard treatment used in the trial. By doing this, we will test whether SETD7 levels can help predict which patients benefit most from immunotherapy.

Our goal is to determine whether SETD7 could serve as a biomarker, meaning a biological signal that helps doctors choose the best treatment for each patient. If we find that SETD7 can identify which patients are more likely to respond to immunotherapy, this could lead to more personalized kidney cancer care. It may help patients receive treatments that are more effective for them while avoiding unnecessary side effects from treatments that are unlikely to work.