Study Finds Radiation Remodels T-Cell Responses in Patients with RCC

Research published in PNAS, the Proceedings of the National Academy of Sciences of the United States of America, demonstrated for the first time that radiation remodels T-cell responses found within the tumors of patients with renal cell carcinoma (RCC), a form of kidney cancer that was previously thought to be radiation-resistant.

In an interview with CancerNetwork®, senior author Jason Muhitch, PhD, assistant professor of Oncology in the Departments of Urology and Immunology at Roswell Park Comprehensive Cancer Center, discussed the study findings and how this research could possibly impact practice guidelines for this patient population moving forward.

CancerNetwork®: Can you explain the key highlights of the study?

Muhitch: Our team studied kidney tumors resected after radiation treatment to uncover how this therapy influences patient antitumor immune responses. Analysis of the intratumoral T-cells revealed that tumors treated with radiation had a more clonal T-cell repertoire compared to patient tumors that were only resected. By identifying the intratumoral T-cell clones through high-throughput sequencing, we revealed that these same clones were expanded 2 weeks after radiation in peripheral blood samples. Interestingly, these same tumor-enriched T-cell clones were contracted in peripheral blood samples taken 4 weeks after radiation.

What would you say are the implications of these study findings?

The observed phases of expansion and contraction in patient peripheral blood samples could indicate a window in which radiation promotes T-cell activation and expansion, which is restrained relatively quickly. These same T-cell clones may also be actively infiltrating the tumor and the observed changes in peripheral blood may represent a combination of these processes. To decipher the relative contributions of T-cell activation and infiltration to the observed changes in peripheral blood will clearly require additional studies.

How could these study findings change practice guidelines in the future?

There are dozens of open clinical trials evaluating the combination of radiation regimens with various forms of immunotherapy. As the field learns more about the mechanisms of action and biomarkers of immune-based treatments, we are likely to improve design and rationale to benefit patients. The study findings in kidney cancer patients at a specific radiation dose reveal that there may be a window of expansion that could be leveraged with certain types of immunotherapy, but additional work is required.

Are there any sort of planned next steps for the study?

Whether specific radiation doses heighten, or limit patient antitumor immune responses is a longstanding question in the field. Future studies will evaluate the influence of radiation dose and scheduling on patient antitumor immunity.

For patients who may not understand these findings, how would you explain the study findings in lay terms?

By studying the effects of radiation and immunotherapy on the immune cells of people treated for kidney cancer, we learned that we may be able to improve the effectiveness of this treatment combination through careful timing or sequencing of the treatments.

Reference:

Chow J, Hoffend NC, Abrams SI, Schwaab T, Singh AK, Muhitch JB. Radiation induces dynamic changes to the T-cell repertoire in renal cell carcinoma patients. PNAS. doi: 10.1073/pnas.2001933117/-/DCSupplemental