“It will allow us to define KS tumor cells with unprecedented precision,” Warren said. “To my knowledge, this has never been done before.”
This is the kind of state-of-the-art tumor analysis that is becoming commonplace in advanced laboratories like the Hutch, but out of reach in most of Africa. Warren and his Global Oncology team hope their findings will lead to improved treatments for Ugandans with KS, as well as for the approximately 1,000 Americans who are diagnosed with the disease each year, primarily in areas where HIV stigma or lack of access to care delays diagnoses.
According to Dr. Tom Uldrick, deputy head of Global Oncology, the number of new KS cases in the U.S. has dropped about 80 percent since the early days of the AIDS epidemic. Yet it remains a problem for those who are HIV positive. “It is the No. 2 cancer among people with HIV (behind lymphoma) in this country,” Uldrick said.
New laboratory techniques such as single-cell RNA sequencing are needed to gain a better understanding of KS, because this cancer has proven difficult to study using the kinds of analyses that have been standard since the 1980s.
“You can’t even really study Kaposi sarcoma that well in a petri dish,” Uldrick said.
For example, KS is triggered by infection of cells lining blood and lymph vessels with human herpesvirus 8, which preys on individuals whose immune systems are weakened by HIV, age or illness. But HHV-8 will not grow in laboratory-cultured samples of KS cells.
Fred Hutch researcher Dr. Warren Phipps, medical director of the UCI-Fred Hutch collaboration and a specialist in KS, spends most of his time each year in Kampala working with Ugandan physicians and treating patients. Over his 10 years working in Uganda, Phipps has established one of the largest cohorts of KS patients in the world. He and his team perfected the art of removing KS tumor samples as they established a collection of biopsies from more than 1,000 tumors obtained from their patients in Uganda. The effort to bring living KS tumor cells from Kampala to Seattle is the latest advance building on the decade of research on KS at UCI-Fred Hutch.
Long before HIV emerged as a global pandemic and made infected people vulnerable to KS, that cancer was relatively common in Uganda, where about 70 percent of the population carries HHV-8. Today, about 10–15 percent of KS cases in Kampala are diagnosed in patients who are HIV-negative, and researchers there are seeing more HIV patients diagnosed with the cancer despite being on antiretroviral drug therapy.
“We see a lot of people presenting with advanced KS disease, and we still have relatively poor outcomes here,” Phipps said. About half the patients die within a year of diagnosis. “We need novel therapies and 21st-century technologies to understand who might respond best to which therapies,” he said.
Phipps believes the advanced research now made possible by shipping living tumor and immune cells to Seattle could be pivotal in helping researchers understand the peculiarities of KS tumors in Africa. Single-cell analysis has the potential to spotlight rare immune cells that are effective in the body’s defensive response to viruses or to damaged cells that could become malignant.
“We can see things that would otherwise be lost. We can pick out patterns that also would be lost,” Phipps said, “and what we learn from KS will have lots of application to other tumors.”
The Global Oncology team includes Towlerton and lab operations manager James Ferrenberg, based at Fred Hutch; and laboratory director Dr. Britta Flach and researchers Lazarus Okoche and Diana Basemera in Kampala. The team sees this effort to bring live tumor and immune cells to Seattle as a short-term step. Their long-term aim is to supply these highly trained Ugandan partners with their own high-speed cell-sorting and gene-sequencing equipment in Kampala, so they can pursue their own research where they feel it would bring the most benefit.
“I know our patients here are supportive,” Phipps said in a phone call from Kampala. “They are looking for better treatments. They are looking for answers.”