Not all kidney cancers behave in the same way, with very different responses to immunotherapy or other treatments, and with very different outcomes for patients.

By sequencing the RNA of individual cells from multiple benign and cancerous kidney tumors, researchers at the Rogel Cancer Center at the University of Michigan (United States) have identified the cells from which the different subtypes originate, the pathways involved and the way where the tumor microenvironment influences cancer development and response to treatment.

The findings, published in the journal PNAS, could help researchers better understand what forces influence renal cell carcinoma and guide oncologists in selecting the best treatment for each patient.

“Single-cell RNA sequencing was key in allowing us to monitor gene expression patterns in each individual cell, revealing the mechanisms at play within the tumor microenvironment that can predict overall survival,” says study author Dr. Arul Chinnaiyan, director. of the Michigan Center for Translational Pathology and professor of pathology at Michigan Medicine.

The researchers generated gene expression atlases from normal kidney and renal cell carcinoma samples. They predicted the putative cell of origin of more than 10 renal cell cancer subtypes. The analysis also revealed pathways and interactions within the tumor microenvironment that predicted whether the tumor would respond to immunotherapy. This could lead to biomarkers that help guide kidney cancer treatment.

“Knowing the type of cell in which a cancer originates can allow us to direct more precise treatments for that type of cancer, as well as better understand the response to therapy,” says Chinnaiyan.

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