New research from the Johns Hopkins Kimmel Cancer Center reveals that tertiary lymphoid structures (TLS) found in liver tumors post-immunotherapy may serve as crucial markers for treatment response and long-term patient outcomes. The study, published in Nature Immunology, sheds light on these structures' role in enhancing anti-tumor immunity.
The Role of Tertiary Lymphoid Structures
Lymph nodes are vital to the immune system, facilitating immune cell interaction and response to pathogens. TLS, highly organized collections of B and T cells reactivated by ICI therapy, form in non-lymphoid tissues due to chronic inflammation or tumorigenesis. Unlike regular lymph nodes, TLS develop in response to specific immunological stimuli, such as cancer or infection.
The study identifies a previously unrecognized form of TLS in hepatocellular carcinoma (HCC) that emerges following presurgical immunotherapy. These structures appear to enhance anti-tumor immunity, leading to a decrease in cancer recurrence rates after surgical intervention.
Clinical Implications and Findings
"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," said senior study author Mark Yarchoan, MD, an associate professor of oncology at the Johns Hopkins School of Medicine.
The investigators analyzed biopsies from HCC patients treated with ICIs and found that patients exhibiting a higher prevalence of TLS were more likely to experience tumor shrinkage and lower rates of cancer recurrence post-surgery.
Notably, tumors that developed these structures centrally, rather than peripherally, showed the most significant response to treatment, indicating that their location and structure may help determine patient outcomes.
Transformation of TLS
According to the study’s lead author, Daniel Shu, MD, now a professor at the University of Maryland Medical School, there is a distinct transformation of TLS in patients who responded favorably to immunotherapy. This form is characterized by a dispersion of B cells, alongside a retention of T cell zones, which may be critical for sustained immune activation against tumors.
Future Directions
While the new research can help clinicians better determine outcomes prior to surgery for HCC patients, it also points to finding ways to induce the formation of tertiary lymphoid structures in patients that don’t respond, as a method to improve the efficacy of ICI treatment.
The new findings also suggest further investigation into how combinations of immunotherapies or other presurgical therapies might impact the formation and functionality of tertiary lymphoid structures, potentially benefiting patients across multiple cancer types.
