Winship study sheds light on immune control of cancer
Woodruff Health Sciences Center | Dec. 11, 2019
Winship/Vaccine Center researchers collaborated with surgeons to investigate how the level of T cell infiltration in tumors can predict post-surgery outcomes.
From left to right: Carey Jansen, Nataliya Prokhnevska, Haydn Kissick and Viraj Master
New findings could provide doctors with vital clues about how the immune system prevents cancer from recurring.
The study from Winship Cancer Institute of Emory University looked at whether immune cells were present in tumor samples removed from patients with kidney and other urologic cancers. For those patients where the immune system had effectively infiltrated the tumor, they experienced a longer time without the progression of their cancers after surgery, the study found.
The results, published Wednesday in Nature, could also help doctors expand and better target the use of immunotherapy, which has been found to have dramatic results in some patients. The researchers focused on kidney and other urologic cancers but they say the results could apply more broadly to other cancer types.
“We knew that if there are more T cells in a tumor, the patient is likely to respond better to cancer immunotherapy,” says lead author Haydn Kissick, PhD. “But we were looking at a more basic question: why do some tumors have lots of T cells in them, and others don’t?”
Kissick is assistant professor of urology and microbiology and immunology at Emory University School of Medicine, Emory Vaccine Center and Winship Cancer Institute. His lab collaborated with surgeons and oncologists at Winship to examine tumor samples removed from patients with kidney, prostate and bladder cancer.
The researchers found that the immune system establishes “forward operating bases”, or lymph node-like structures, inside the tumors of some patients. Those with well-supported immune outposts in their tumors were more likely to control their cancers’ growth for a longer time.
CD8 T cells hunt down and eliminate intruders – in this case, cancer cells. In patients with high levels of CD8 T cells residing in their tumors, their immune systems appeared to be better trained to suppress cancer growth after surgery, when small numbers of cancer cells (micrometastases) may be lurking elsewhere in the body. The cancers of those who had lower levels of CD8 T cells tended to progress four times more quickly after surgery than those with higher levels.
The finding has important implications, says Viraj Master, MD, who performed most of the kidney cancer surgeries. In this situation, additional treatments are not performed unless or until kidney cancer reappears, says Master, who is Fray F. Marshall chair and professor of urology at Emory University School of Medicine and Winship’s Director of Integrative Oncology and Survivorship.
“Even after potentially curative surgery for aggressive kidney cancers, a significant fraction of patients will experience cancer recurrence,” he says. “But with this information, we could predict more confidently that some people won’t need anything else, they care cured – thus avoiding overtreatment. However, others who are at higher risk of recurrence on the basis of these findings, we could potentially scan at more regular intervals, and ideally, design adjvant therapy trials.”
The findings also provide insights for scientists interested in how the immune system successfully controls some cancers, but with others, the T cells become increasingly exhausted and ineffective.
“This study may lead to new insights into why immunotherapy can be so effective in some cancer types, but rarely works in others such as prostate cancer, and may highlight a path forward for developing more effective immunotherapy treatments,” says Howard Soule, PhD, executive vice president and chief science officer for the Prostate Cancer Foundation, which supported the Winship team’s work.
The first author of the paper is MD/PhD student Carey Jansen. Additional co-authors include: graduate student Nataliya Prokhnevska, urology chair Martin Sanda, MD and biostatistician Yuan Liu, PhD.
The research was supported by the National Cancer Institute (R00CA197891, U01CA113913), the Prostate Cancer Foundation, Swim Across America, the James M. Cox Foundation, James C. Kennedy, the Dunwoody Country Club Senior Men’s Association and an educational grant from Adaptive Technologies.