Gene Expression in Renal Cell Carcinoma May Identify Non-Responders to Nivolumab

A recent study found that patients with renal cell carcinoma (RCC) positive for PD-L1 who did not respond to treatment with nivolumab may have a different gene expression profile than those who responded to the treatment.

They discovered that patients who did not respond to the anti-PD-1 treatment had a higher expression of genes associated with metabolism, according to a study published by Cancer Immunology Research.

“Given that nivolumab works by releasing the brakes on the immune system, most studies of treatment resistance so far have focused on looking for immune system-related mechanisms," said researcher Suzanne L. Topalian, MD. “Our data suggest that resistance can also be caused by tumor-specific mechanisms.”

Included in the study were tumor samples from 13 patients with metastatic RCC positive for PD-L1, and who had not yet received treatment. These patients then received nivolumab in clinical trials. Only 4 of the patients included responded to the treatment.

In the current study, researchers identified 110 genes with elevated expression in tumor samples from the nonresponding patients. Researchers found that a majority of the genes were associated with metabolism, and were also found in cultured kidney cancer cells, according to the study.

By identifying markers that can predict treatment response, researchers believe it can save patients time and prevent side effects.

They state that the small number of patients included is a limitation of the study, but they plan to study larger groups of patients in the future.

“In this study, we found high expression levels of metabolic genes in PD-L1-positive renal cell carcinomas from patients who did not respond to nivolumab. If these data are reproduced in larger groups of patients, we could potentially use the information to guide treatment decisions for patients with renal cell carcinoma,” concluded Dr Topalian. “Given the success of our unbiased whole-genome expression profiling approach, we are looking to extend these studies to analyze other types of cancer, as well as to confirm our current results in additional renal cell carcinomas from patients receiving anti-PD-1 therapies. Such studies may also reveal new drug targets for combination therapies with anti-PD-1.”