Why does this work matter? A rare cancer needs subtype-specific answers.

Chromophobe renal cell carcinoma (RCC) is biologically different from the most common form of kidney cancer – clear cell RCC. Most chromophobe RCC tumors grow slowly, but a smaller group develops aggressive features, including sarcomatoid change, and may spread. Because chromophobe RCC is rare, any single institution may have too few samples to see the full pattern.

The KCA and Tempus collaboration helps close that gap. It combines a large, de-identified clinicogenomic data resource with tissue analysis, spatial biology, and laboratory models. The researchers then ask whether signals identified in the data can be tested experimentally.

KCA x Tempus Research Collaboration

The KCA partnered with Tempus to support a two-year postdoctoral research fellowship focused on accelerating kidney cancer research through data science, artificial intelligence, and precision medicine.

Nathan D. Maulding, PhD, served as the inaugural KCA-supported postdoctoral fellow at Tempus. He led computational analyses connecting genomic changes, gene-expression programs, and clinical features across chromophobe RCC and other cancer types.

Tempus scientific leads Andrew J. Sedgewick, PhD, and Justin Guinney, PhD, provided scientific mentorship, analytical expertise, and access to Tempus’ de-identified multimodal data and research platform.

Clinical and laboratory investigators included Niki Zacharias Millward, PhD; Pavlos Msaouel, MD, PhD; Elizabeth Ellis, MD; and Elizabeth Henske, MD. They connected the data signals to chromophobe RCC biology, pathology, patient-derived models, and clinically meaningful research questions.

Patient advocate Gigi Cohen and KCA Chief Scientific Officer Salvatore La Rosa, PhD, helped anchor the fellowship in patient priorities and a broader strategy for rare kidney cancer research. The fellowship was supported by Gigi Cohen and Michael Levin.

The conference studies also included multidisciplinary co-authors from Tempus, MD Anderson Cancer Center, Brigham and Women’s Hospital, Harvard Medical School, and Indiana University.

PROJECT 1: CHROMOSOME INSTABILITY AND TRIP13

Finding a possible driver of aggressive disease

The team analyzed targeted DNA, whole-transcriptome RNA, and clinical information from 168 de-identified chromophobe renal cell carcinoma samples. Tumors with changes in TP53—a gene that normally helps protect the genome—showed high genomic instability and sarcomatoid changes. Sarcomatoid chromophobe RCC had much higher activity of TRIP13, a gene involved in cell division and chromosome control.

Key findings

• TP53 mutations were found in 76 of 168 samples, or 45% of the analyzed cohort.
• Tumors with TP53 mutations had significantly higher genomic instability than tumors without TP53 mutations.
• Higher TRIP13 activity was associated with stage 4 disease, distant metastasis, sarcomatoid chromophobe RCC, and a gene-expression signature linked to chromosome instability.
• TRIP13 was enriched in samples with multiple copy-neutral loss-of-heterozygosity events, a form of genomic alteration in which genetic diversity is lost without a change in the total number of chromosome copies.
• In chromophobe RCC laboratory models, reducing TRIP13 lowered cancer-cell proliferation, migration, and invasion.
• In a mouse model, tumors treated with the experimental TRIP13 inhibitor DCZ0415 grew less and had lower tumor mass than tumors treated with a control vehicle.
• In cell studies, TRIP13 inhibition reduced abnormal multipolar spindle formation during cell division.

What the findings could mean

TRIP13 may be a marker of aggressive chromophobe RCC. It may help cancer cells tolerate errors during division and contribute to aggressive behavior. The laboratory results make TRIP13 a candidate for further validation, but it is not yet a proven drug target or treatment for people with chromophobe RCC.

PROJECT 2: THE IMMUNE MICROENVIRONMENT

Mapping immune cells inside aggressive tumors

A second research team compared classic and sarcomatoid chromophobe RCC using spatial transcriptomics, a method that measures thousands of RNA signals while preserving information about where those signals occur within the tissue.

The spatial analysis included 10 tumors: six classic, three sarcomatoid, and one containing both components. The team also analyzed Tempus RNA data from 113 primary and 27 metastatic chromophobe RCC tumors.

Key findings

• Sarcomatoid chromophobe RCC showed a more immune-infiltrated tumor environment than classic chromophobe RCC.
• T cells and macrophages were present within sarcomatoid tumor regions.
• T cells in sarcomatoid tumors showed higher expression of immune checkpoint genes, including CTLA4 and LAG3.
• Metastatic samples showed higher LAG3 expression than primary kidney tumors.
• Metastatic samples also showed enrichment of gamma-delta T cells, a distinct type of T cell.

What the findings could mean

Aggressive chromophobe RCC may not be uniformly “immune cold.” Immune-rich tumor regions and increased checkpoint signals offer hypotheses for future treatment studies. However, the spatial analysis involved a small number of tumors, and the findings require confirmation in larger, independent cohorts.