New combination therapy helps fight cancer

Radiation causes key changes to immune cells in kidney cancer tumors.T cells in tumors are expanded in blood shortly after radiation, then decrease. Study shows the timing of treatments may improve the success of cancer immunotherapy.

It's clear that radiation therapy, or radiotherapy, an approach used to treat cancer since the early 20th century, can be an effective companion to newer, immune-stimulating approaches known as immunotherapy.

Research from a team from Roswell Park Comprehensive Cancer Center explains how radiation helps boost the immune system's ability to fight cancer in combination with immune checkpoint inhibitors -; and provides new evidence that the timing of these therapies can make a big difference in how effectively they work together.

While more than 100 clinical trials currently underway are exploring the combination of radiation with immunotherapy, little is known regarding radiation's impact within the tumor microenvironment. Looking to fill that void, the researchers, led by Jason Muhitch, Ph.D., Jacky Chow, Ph.D., and Anurag Singh, MD, focused their study on renal cell carcinoma (RCC), a form of kidney cancer that, until a few years ago, was thought to be radiation-resistant.

In new research published today in PNAS, the Proceedings of the National Academy of Sciences of the United States of America, they show for the first time that radiation remodels T cell responses found within patient tumors.

Based on results of high-throughput sequencing of samples from patients with RCC, the researchers found that stereotactic body radiation therapy, or SBRT, led to expansion of peripheral blood T cell clones that were also found within patient tumors -; the first report of this dynamic in any cancer type.

Interestingly, this expansion was short-lived, and we saw contraction or reduction of these T cell clones when we evaluated peripheral blood four weeks after treatment. That suggests that we have a window shortly after radiation treatment to improve patient outcomes using combination strategies with immunotherapy."

Jason Muhitch, PhD, Study Senior Author and Assistant Professor of Oncology, Departments of Urology and Immunology, Roswell Park Comprehensive Cancer Center

The work reveals new dynamics of human immune responses, with two important implications: (1) single-dose radiation is an effective immune-sensitizing agent for patients with RCC, and (2) timing is a critical factor for combination strategies that rely on endogenous T cell responses, or activation of immune cells within organs.

"Our findings help explain how a conventional cancer treatment can bolster immune responses in kidney cancer patients," says Dr. Muhitch, "and may point the way to better treatment outcomes for more patients -; not just in kidney cancer, but for other cancer types too."

Source:
Journal reference:

Chowa, J., et al. (2020) Radiation induces dynamic changes to the T cell repertoire in renal cell carcinoma patients. PNAS. doi.org/10.1073/pnas.2001933117.

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