Researchers have found that spatial tissue analysis may help predict early posttreatment relapse and illuminate new potential therapies in patients with high-grade serous ovarian carcinoma, according to a recent study published by Xu et al in Science Advances.
Background
Many patients with ovarian cancer may respond to initial treatment with surgery and chemotherapy but subsequently experience cancer recurrence. High-grade serous ovarian carcinoma is the deadliest type of ovarian cancer.
Mass cytometry is capable of revealing the spatial protein content of tissue.
Study Methods and Results
In the recent study, the researchers used mass cytometry to analyze the tissue samples of 42 patients with high-grade serous ovarian carcinoma with primary or recurring tumors. They focused on plasma cells to determine the tumor immune response.
“Using spatial protein analysis, we looked not only at the types of cells within and around a tumor, but also at their relative positions and how they interact,” explained lead study author Alex Xu, PhD, a research scientist at Cedars-Sinai Cancer and the Board of Governors Regenerative Medicine Institute at Cedars-Sinai.
The researchers discovered patterns consistently associated with patients whose cancer relapsed soon after treatment. They also found that outcomes correlated with the location of the plasma cells and their relationship with adjacent cell types.
“Plasma cells were associated with [positive] patient outcomes when lymphoid aggregates…, structures that include T and B cells, were also abundant in the area immediately surrounding the tumor. This could be because the plasma cells were part of these organized structures that facilitated communication between these immune cells, thus improving their ability to attack the tumor,” Dr. Xu detailed.
Plasma cells were linked with negative patient outcomes when cancer-associated fibroblasts—known to interfere with the activity of immune cells—were abundant, suggesting that fibroblasts may prevent plasma cells from communicating with other immune cells.
Conclusions
“Spatial analysis is the next frontier in tissue biomarker development, and our group has demonstrated the importance of spatial analysis in several cancer types,” underscored co–senior study author Akil Merchant, MD, Director of the Spatial Molecular Profiling Core facility at Cedars-Sinai Cancer.
“Our findings suggest that plasma cells are a clinically important factor determining a patient’s time to relapse,” emphasized Dr. Xu. Previous research into their role has been contradictory, with some studies suggesting their presence predicted negative outcomes while others suggested positive outcomes,” he added.
“These different microenvironments could account for sometimes differing reports about the role of plasma cells in patient prognosis,” proposed Dan Theodorescu, MD, PhD, Director of Cedars-Sinai Cancer and the Phase ONE Distinguished Chair at Cedars-Sinai. “This avenue of investigation could help us identify biomarkers, or even precision therapies, that improve outcomes for patients with this particularly deadly cancer,” he concluded.
Disclosure: The research in this study was supported in part by the U.S. Department of Veterans Affairs Merit Awards; the Office of the Assistant Secretary of Defense for Health Affairs through the Ovarian Cancer Research Program Award; the Sandy Rollman Ovarian Cancer Foundation; and grants from the National Institutes of Health (NIH) and the NIH National Center for Advancing Translational Science University of California, Los Angeles Clinical and Translational Science Institute. For full disclosures of the study authors, visit science.org.
