Therapeutic potential of tumor-infiltrating lymphocytes (TILs) derived from metastatic lymph nodes in advanced cervical cancer

Overcoming the Challenges of Advanced Cervical Cancer

Cervical cancer remains a global health burden, with over 570,000 new cases and 311,000 deaths annually. Existing treatment options for advanced stages, such as chemotherapy and checkpoint inhibitors, yield limited efficacy, with response rates often below 36%. The innovative approach of adoptive TIL therapy, as showcased in this study, holds the potential to shift treatment paradigms.

Breakthrough Case: Efficacy of GT101 Therapy

The study highlights the clinical course of a patient with recurrent metastatic cervical cancer, treated with autologous TILs (GT101) alongside interleukin-2 (IL-2) following a modified lymphodepleting regimen. Key outcomes included:

1. Partial Response (PR): Significant regression of metastatic lesions post-infusion (Figure 1).
2. Durable TIL Expansion: TCR sequencing revealed robust engraftment and persistence of dominant TIL clones in peripheral blood over two months.

Manageable Safety Profile: Immune-related adverse events (irAEs), such as fever and hypotension, were transient and tolerable.

Implications for Clinical Practice and Future Directions

This study underscores the feasibility of using metastatic lymph nodes as ideal sources for high-quality TIL production. Attributes such as a balanced CD4/CD8 ratio, enriched memory phenotypes, and stem-like CD8⁺ subsets may contribute to the observed therapeutic efficacy. The findings set the stage for larger clinical trials to validate the efficacy of TIL therapy in broader patient populations. Additionally, future study in the antigenic targets of dominant TCR clones could facilitate the development of tumor specific TCR-enriched TIL products for further improvement of therapeutic efficacy.

Conclusion

This pioneering work highlights the transformative potential of TIL therapy in the treatment of patients with refractory cervical cancer. The collaborative efforts of the First Affiliated Hospital of Zhengzhou University and Grit Biotechnology exemplify the critical role of translational research in advancing cancer care.

Digital Object Identifier (DOI): 10.1186/s43556-024-00215-w

Related Journal Name: Molecular Biomedicine