Researchers may have shed light on how radiation therapy impacts immune cells and tumor cells in renal cell carcinoma, according to a novel study published by Chow et al in the Journal for ImmunoTherapy of Cancer. The new findings may provide key information for planning treatment regimens that combine immunotherapy and radiation therapy.
Background
Renal cell carcinoma is the most common type of kidney cancer in adult patients.
Previously, researchers knew little about how radiation therapy targeting cancer cells may affect immune cells and other tumoral components.
“There’s a lot of interest right now in combining radiation … with immune-based treatments to try to improve responses to immunotherapy,” explained senior study author Jason Muhitch, PhD, Assistant Professor of Oncology in the Department of Immunology at the Roswell Park Comprehensive Cancer Center. “If we know more about how radiation works by itself, we can better combine it with different forms of immunotherapy,” he added.
Study Methods
In the new study, the researchers utilized single-cell RNA sequencing and spectral flow cytometry in patients with renal cell carcinoma to analyze their tumors and better understand the changes that occur with radiation therapy. Among the patients involved in the study, eight of them had been treated with nephrectomy without radiation. Six of them had previously participated in a clinical trial (ClinicalTrials.gov identifier NCT01892930) in which they underwent a nephrectomy after treatment with stereotactic body radiation therapy to target their tumors precisely with very high doses of radiation.
To identify differences in both the immune cells and tumor cells of patients in both groups, the researchers performed the spectral flow cytometry—which makes it possible to detect specific subtypes of immune cells and describe the changes taking place within those subtypes dependent on the type of treatment. They then performed a single-cell RNA sequencing analysis to reveal the programming of individual immune and tumor cells and how that code may have changed after radiation therapy.
The researchers discovered that irradiated tumors contained higher levels of both early-activated and “exhausted” CD8-positive T cells, which have been weakened by previous activity. They noted that their findings may provide clues regarding how these CD8-positive T cells could be employed to treat tumors.
Conclusions
“A more widely used form of immune checkpoint inhibitor, anti–PD-1 therapy, might work very well for unleashing more of the antitumor effects of these exhausted CD8 T cells that we’re seeing increased after radiation,” said Dr. Muhitch. “And when we look at just the tumor cells, we can see from their expression patterns that they are more susceptible to the cytotoxic killing effects of the T cells. There’s an advancement here in terms of understanding what effects radiation [therapy] has on both T cells and cancer cells within patient tumors. That information is powerful,” he said.
The researchers brought those two pieces of information together and predicted that radiation therapy may increase the interactions between the T cells and the tumor cells. They have since made their high-dimensional study data freely available in public repositories so members of the wider research community can use them in future studies.
“We tried to learn as much as we could using state-of-the-art technology to inform us about the changes that occur in patient tumors that are treated with radiation [therapy]. Those precious cells may help another patient [with cancer] in the future,” Dr. Muhitch concluded.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.
