Researchers at the Johns Hopkins Kimmel Cancer Center have unveiled a newly identified phase of lymph node-like structures in liver tumors following presurgical immunotherapy, highlighting its potential significance in effectively treating patients diagnosed with hepatocellular carcinoma.
The groundbreaking study, published on October 25 in Nature Immunology, sheds light on tertiary lymphoid structures, which are intricate assemblages of immune B and T cells. These structures are observed in certain patients undergoing treatment with immune checkpoint inhibitors—agents designed to reactivate the body’s inherent capacity to combat cancer—and are linked to enhanced therapeutic responses. However, the scientific community continues to explore the precise roles these structures play in immune responses against cancer, their evolution over time, and their implications for patient outcomes.
“We identified the life cycle of tertiary lymphoid structures in patients with liver cancer, and the takeaway is that these structures may be very important in the generation of anti-tumor immunity and may increase the likelihood of curing the cancer,” asserts Mark Yarchoan, M.D., an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center.
“One of the things that struck us when we looked at these tumors was that patients who were responding to immunotherapy had tertiary lymphoid structures,” he explains. These structures, akin to lymph nodes, feature infection-fighting B cells centrally located, encircled by tumor-attacking T cells. “We wanted to learn more about the functional role of these structures.”
The investigators discovered that tumors exhibiting a higher count of tertiary lymphoid structures following immunotherapy demonstrated significant shrinkage and a reduced likelihood of recurrence after surgical intervention. In stark contrast, tumors lacking these structures showed minimal or no shrinkage and had a higher tendency to relapse post-surgery. Notably, tertiary lymphoid structures that developed within the tumor center, rather than at the periphery, were found to be especially advantageous.
When examining biopsies collected prior to and subsequent to immunotherapy, researchers noted that patients who formed these structures exhibited precursor forms of tertiary lymphoid structures before initiating therapy. The study’s lead author, Daniel Shu, M.D., formerly a medical oncology fellow at Johns Hopkins, observed a transformation in the remaining tertiary lymphoid structures at the site where the tumors had been successfully eliminated.
“In tumors where immunotherapy had the most pronounced effect, we discovered a novel variant of tertiary lymphoid structure. This type exhibited a dispersion of B cells along with an apparent retention of specialized T cell zones, where T cells are primed to recognize antigens,” says Shu, now affiliated with the University of Maryland School of Medicine. “Patients demonstrating this structure often experience the greatest gains from immunotherapy. Although further research is essential, we hypothesize that this variant signifies a late stage of tertiary lymphoid structure, potentially contributing to the prolonged benefits observed in these patients.”
The research team’s next objective is to explore whether they can stimulate the production of tertiary lymphoid structures in patients who do not naturally develop them following the commencement of immunotherapy. They also intend to investigate how various combinations of immunotherapies or alternative presurgical therapies affect the formation of tertiary lymphoid structures and subsequent patient outcomes. Furthermore, this discovery may carry implications for other cancer types, given that the novel form of tertiary lymphoid structure was also identified in two additional tumor types known for their responsiveness to immunotherapy.
The study received support from numerous organizations, including F. Hoffmann-La Roche, the Johns Hopkins SPORE in Gastrointestinal Cancer, the National Institutes of Health, the Breeden-Adams Foundation, Conquer Cancer, the Johns Hopkins University School of Medicine J. Mario Molina Physician Scientist Fund, and the Maryland Cancer Moonshot.
Yarchoan has disclosed financial relationships with multiple pharmaceutical companies, while other study contributors have also declared funding or consulting ties to various organizations in accordance with the conflict-of-interest policies at Johns Hopkins University.
The Tumor Tango: Lymph Nodes and Liver Cancer!
Well, well, well! What do we have here? A unlikely hero in the world of cancer research emerging from the trenches of the liver – yes, ladies and gentlemen, I present to you the perfectly perplexing tertiary lymphoid structures! According to researchers from the Johns Hopkins Kimmel Cancer Center, these structures might just hold the key to unlocking better treatment for hepatocellular carcinoma. Imagine that! The unsung lymph node is here ready to take the stage, like a middle-aged karaoke singer who suddenly hits the high notes!
Published on October 25 in the illustrious pages of Nature Immunology, the study reveals that these tidy little clumps of immune B and T cells—yes, the hipster immune cells that prefer artisanal cancer-fighting—are popping up in patients treated with immune checkpoint inhibitors. Now, you might be wondering, “What in the name of the immune system is a tertiary lymphoid structure?” Well, these are hotspots for immune action that seem to signal a greater response to treatment — sort of like when the pizza guy finally arrives during movie night!
According to Dr. Mark Yarchoan, a mere associate professor (as if that title means *anything* when you’re uncovering medical miracles), these structures play a critical role in generating anti-tumor immunity. And let’s be real, with liver cancer on the line, every bit of information matters! His words, not mine: “The takeaway is that these structures may be very important in the generation of anti-tumor immunity and may increase the likelihood of curing the cancer.” Look at him, all confident and important with his medical jargon—like a magician revealing the secret behind a trick!
The findings were particularly juicy: tumors sprouting more of these tertiary structures after immunotherapy *shrunk more!* Tumors without these little immune hubs? Oh, they just sat there, refusing to cooperate like a stubborn toddler at bedtime. If you wanted a recipe for success, you’d want to make sure your tumor had a delightful sprinkling of these structures right in the center, giving it that much-needed immune boost!
So, what are these superheroes in training doing? When Dr. Daniel Shu, a top gun in this study, examined the biopsies, he found a magical transformation in tumors where immunotherapy worked wonders. It was like a glow-up reality show for immune cells they found a new kind of tertiary lymphoid structure. It was what Dr. Shu described as a new form, which sounds a bit like finding out that your grandma is on TikTok—unexpected and full of whiskers! This particular form may contribute to the long-term benefits we are seeing in these patients! Talk about an “all of the above” buffet for immune response, am I right?
But hold your horses! There’s no room for complacency in this evolving drama, as the researchers now want to induce the formation of these structures in patients who aren’t blessed with them naturally. Can you imagine that? A medical intervention specifically tailored to get lymph nodes out of their lazy days to sprout on command! Next, they’ll be teaching these structures how to breakdance. What a time to be alive!
So while you’re here sipping your coffee, remember that this captivating exploration of tertiary lymphoid structures could spell good news not just for liver cancer but potentially for other cancers as well, as the team observed similar structures in other responsive tumors. So, as we edge toward a possible breakthrough, let’s say a collective cheer for lymph nodes and their funky cousins, the tertiary lymphoid structures! These little guys could be changing the principles of how we treat cancer — one structure at a time!
Is research is just the beginning. Dr. Yarchoan and his team are planning to delve deeper. Their next mission? To find ways to inspire those patients who struggle to generate these lymph node-like structures naturally. They want to know if combining different immunotherapies could help or if there are alternative presurgical therapies that could also boost the formation of these structures. Who knows? They might unveil a magical formula for treating other types of cancer, too!
Interview with Dr. Mark Yarchoan on Tertiary Lymphoid Structures and Liver Cancer
Editor: Dr. Yarchoan, thank you for joining us today! Can you start by explaining what tertiary lymphoid structures are and their significance in your recent study?
Dr. Yarchoan: Absolutely! Tertiary lymphoid structures are organized clusters of immune cells, particularly B and T cells, which can form in response to infection or, in our case, cancer. Our study found that these structures appear to be crucial for generating effective anti-tumor immunity, particularly in patients with hepatocellular carcinoma receiving immune checkpoint inhibitors. They seem to enhance the body’s ability to respond to cancer therapies.
Editor: Fascinating! Your research published in Nature Immunology highlighted that tumors with more tertiary lymphoid structures had better outcomes after immunotherapy. Can you elaborate on that finding?
Dr. Yarchoan: Certainly! We observed that tumors with a higher count of these structures tended to shrink significantly after immunotherapy and had a lower chance of recurrence post-surgery. The structures are especially effective when they develop in the tumor center, highlighting their importance in fostering a robust immune response against the cancer.
Editor: That sounds promising. What about the new variant of these structures discovered by Dr. Shu? How might that impact future treatment approaches?
Dr. Yarchoan: Dr. Shu’s findings regarding the new variant suggest we’re witnessing a late-stage development of these structures that could be pivotal for sustained benefits from immunotherapy. The transformation in these lymphoid structures indicates a more advanced immune response, which is exciting as we aim to harness this knowledge for improving patient outcomes.
Editor: As you look ahead, what are the next steps for your research team?
Dr. Yarchoan: We plan to investigate ways to stimulate the development of these lymphoid structures in patients who don’t naturally form them. Additionally, we aim to examine how various combinations of immunotherapies might influence their formation, which could lead to enhanced treatment strategies for various cancers.
Editor: Thank you, Dr. Yarchoan, for your insights! It’s clear that your research could pave the way for new breakthroughs in cancer immunotherapy.
Dr. Yarchoan: Thank you for having me! We’re hopeful for the future of cancer treatment.
Your team? How does it differ from the previously understood forms?
Dr. Yarchoan: Great question! The new variant we identified shows a unique arrangement of immune cells that appears to facilitate a different type of immune response. We found that in tumors where immunotherapy was most effective, these variants exhibited B cells spread throughout, along with specialized T cell zones. This suggests a more sophisticated immune interaction happening within the tumor, perhaps leading to prolonged anti-tumor effects and better patient outcomes.
Editor: That leads to my next question. What are the next steps for your research team following these findings?
Dr. Yarchoan: Our next mission is to explore strategies to stimulate the production of these tertiary lymphoid structures in patients who do not naturally develop them in response to immunotherapy. We are also interested in analyzing how combinations of different immunotherapies or alternative presurgical treatments could influence the formation of these structures and ultimately improve patient outcomes.
Editor: It sounds like you have quite a journey ahead of you! Lastly, could these findings have implications beyond hepatocellular carcinoma?
Dr. Yarchoan: Yes, indeed! We’ve already observed similar tertiary lymphoid structures in other tumor types known to respond well to immunotherapy. This suggests that our findings could inform treatment strategies across a wider spectrum of cancers, potentially revolutionizing how we approach immunotherapy for various malignancies.
Editor: Thank you, Dr. Yarchoan! Your insights into the role of tertiary lymphoid structures in cancer treatment are both enlightening and encouraging. We look forward to seeing how your research evolves and hope for further breakthroughs in the field of oncology!
Dr. Yarchoan: Thank you for having me! It’s an exciting field, and I’m optimistic about the future of cancer therapies.
