Tertiary Lymphoid Structure May Improve Immunity for Patients With Ovarian Cancer

A researcher discusses how developing tertiary lymphoid structures may reach a greater maturity level within the tumor microenvironment.

More mature tertiary lymphoid structures (TLS) may increase CD8+ (cytotoxic) T cells, which can make immunotherapies more effective for patients with ovarian cancer, explained Tullia Bruno, PhD, during a presentation at the 2022 International Cancer Immunotherapy Conference. A self-proclaimedT cell enthusiast, B cell convert,” Tullia Bruno, PhD, noted that the unique tumor microenvironment (TME) is an important factor for immunotherapy, with more mature TLS producing better immunotherapeutic outcomes.

When analyzing her investigative team’s study results, Bruno observed that TLS corelates with improved survival. Additionally, Bruno explained that other studies have confirmed the importance of TLS for survival and immunotherapeutic response. However, she suggests that it is important to also look at the significance of how the TLS functions or assess the mechanisms by which TLS matures to create more effective outcomes.

“I think for that induction, we can’t just think of one factor,” Bruno said. “That’s been the problem with TLS. We have to think about the tumor, we have to think about the stroma, we have to think about the immune microenvironment interaction.”

B cells and T cells are becoming significant when studying immunotherapy, Bruno explained. The aim of her research was to better understanding how to orchestrate these cell interactions, since both are main cell types found in TLS.

Prior to studying this relationship in ovarian cancer, Bruno discussed that her team looked at patients who have head and neck cancer. By imaging and scanning the tissue, they found tumor-specific factors could drive maturation levels in the TLS (which are heterogeneous in the TME).

Following this study, Bruno explained that her team looked at these interactions in ovarian cancer patients. One reason being that, historically, ovarian cancer does not respond well to immunotherapy, with a response rate at approximately 10%. Additionally, ovarian cancer can develop in multiple sites and often originates in the fallopian tube before metastasizing in the ovaries and omentum. Consequently, this can increase potential TMEs.

Furthermore, Bruno explained that results from TLS testing in ovarian cancer versus head and neck cancers showed that TLS are less prominent in high-grade serous ovarian cancer. Looking at TLS levels in ovarian cancer patients, Bruno also explained that there were higher levels of TLS in the fallopian tube (where ovarian cancer often develops first), compared to the TME of the ovaries.

Her lab also looked at activity and maturation of TLS.

“What we wanted to understand is not only the formation, but what pushes those [TLS] cells over to a mature status,” Bruno said. “If the T cell is at the center of the action, they’re not a soloist.”

Bruno explained that her results showed maturity status of TLS is not equal in different TMEs found in ovarian cancer patients. The researchers also identified differences in the tumor and tumor-adjacent regions, which could indicate that that the composition and maturity of TLS can vary by region, thus impacting survival.

Reference

Bruno TC. Harnessing B cell and tertiary lymphoid structure function in ovarian cancer for improved ant-tumor immunity. New York, New York: Sixth International Cancer Immunotherapy Conference 2022; September 29, 2022.