By Steve Blanchard - November 10, 2022
Researchers are getting closer to unraveling the mystery of why the presence of tertiary lymphoid structures, or TLS, at tumor beds predicts better outcome and superior responses to anti-cancer immunotherapy.
The organized clusters of immune cells have long been suspected of participating in the anti-tumor immune response, but the reason behind that has eluded scientists.
A recent study conducted at Moffitt Cancer Center and presented at The Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting & Pre-Conference takes a closer look at TLS and their impact on tumors and usefulness with immunotherapy.
According to Dr. Jose Conejo-Garcia, senior member in Moffitt’s Department of Immunology, the study aimed to define some of the elusive mechanisms of immune protection governed by TLS in human ovarian cancer. The authors first confirmed previous observations that the presence of TLS in ovarian cancer is associated with better outcomes. They then identified antibodies with strong anti-tumor activity that are spontaneously produced in these structures.
"There’s an association with better overall survival among other mechanisms because TLS produces antibodies that limit tumor activities."- Dr. Jose Conejo-Garcia, Department of Immunology
“There’s an association with better overall survival among other mechanisms because TLS produces antibodies that limit tumor activities,” Conejo-Garcia said. “So, we can clone these and better understand what these structures are and perhaps use these antibodies as anti-cancer agents.”
TLS arise in the context of chronic inflammation, such as cancer or autoimmune conditions. Studying these structures through cloning techniques can also clone the antibody produced by the cells, providing better analytics of how it responds to treatment.
Conejo-Garcia said that just because ovarian cancer tumors are used in the study doesn’t mean that information discovered can’t translate to the treatment of other cancers in the future. Bladder cancer, head and neck cancers, melanoma, sarcoma and kidney cancer could benefit from the research.
“Through this, eventually immunotherapies that elicit concurrent T cell and antibody responses will improve and will translate to the most frequent and aggressive human cancers,” he said.
That’s because the presence of TLS has been associated with better responses to immune checkpoint inhibitors in renal cancer, melanoma and sarcoma, among other diseases, according to Conejo-Garcia.
“There may be other mechanisms we didn’t address in the study,” Conejo-Garcia said. “But we can lay out the antibodies produced in multiple patients and clone them.”
Those cloned cells could then be used for therapy purposes.
And that, Conejo-Garcia said, is the take home message.
Learning how TLS are associated with better outcomes will influence advancements in immunotherapy for patients with different types of cancer.
“This is a very hot topic right now because everyone keeps seeing that TLS are associated with protection, but we don’t fully understand why,” he said. “This study provides some clarity and, through that, a better rationale to foster coordinated responses driven by both arms of the adaptive immune response: T cells and B cells, while the field has been narrowly focused on the former. That’s important for improving clinical results.”
For more details on the study, click here.