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Cancer fighting T-cells, the immune system’s primary enforcers, are scarce in the rare kidney cancer called chromophobe renal cell carcinoma (ChRCC) and those that are present are indifferent to the tumor threat and traditional immune therapies, revealing the need for new targets and treatments.
Those are among the results described in a July 2 published report (1) in the Journal of Clinical Oncology that set out to understand the biology of certain kidney tumors, including ChRCC, and their immune responses.
The study found that ChRCC, which accounts for about 5 percent of all kidney cancers, has fewer T-cells and key molecules required for an immune response than other kidney cancers and poorer response and survival rates when treated with immune-based therapies. Oth kidney cancer er examined kidney tumors included in the study were Low-grade oncocytic tumor (LOT) and the usually benign renal oncocytoma (RO).
This study was co-led by other senior others Elizabeth P. Henske, MD of Brigham and Women’s Hospital in Boston, Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, Eliezer M. Van Allen, MD, of Dana-Farber Cancer Institute, and Sachet Shukla, PhD, of MD Anderson Cancer Center. The first author of the study was Chris Labaki, MD, now at the Beth Israel Deaconess Medical Center. It also included several dozen researchers from institutions in the US and Canada.
The study’s detailed machine learning analysis of individual cells from ChRCC tumors, as well as normal tissue, helped determine the origin of the tumor from a specific type of kidney cell, α-intercalated cells.
Researchers identified genes activated or deactivated in ChRCC tumors compared to the original normal cell.
The study further used single-cell sequencing analysis of immune cells in the tumor to learn how ChRCC cancer cells actively hide from the immune system.
While providing new understanding of ChRCC and treatment pathways that could be explored, the study noted limitations, including sample size and the need for further research.
Funding for this work includes the U.S. Department of Defense (award W81XWH-19-1-0550), the US DOD Early Career Investigator Grant (KCRP AKCIECI, W81XWH-20-1-0882), the Kidney Cancer Association (KCA) Trailblazer Award, the Louis Goodman and Alfred Gilman Yale Scholar Fund, the National Institutes of Health, National Cancer Institute (1R37CA279822-01), and the Yale Cancer Center (supported by NIH/NCI research grant P30CA016359). This project was supported in part by a KCRP award the Tuttle Family, and Yale University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
A new study reveals that chromophobe renal cell carcinoma (ChRCC), a rare kidney cancer, avoids immune detection by keeping cancer-fighting T-cells out of the tumor. Unlike other kidney cancers, it doesn't respond to standard immunotherapy because of its unique immune environment. Using machine learning and single-cell analysis, researchers traced the cancer’s origin and uncovered how it hides from the immune system—highlighting the urgent need for new, targeted treatments.
Reference:
1)https://ascopubs.org/doi/10.1200/JCO-25-00234
(Newswise/ MKJ)
