The memory phenotypic immunity of tumor-draining lymph nodes in high-grade serous ovarian carcinoma

The lymphatic system involvement by solid tumors in the peripheral tissues is a hallmark of cancer and often reflects a poor prognosis. Yet, they are strategically positioned at dedicated sites throughout the body to facilitate a rapid and efficient anti-tumor immune response. Emerging evidence suggests that tumor-specific adaptive immune responses occur in the tumor tissue. Still, the contribution of tumor-draining lymph nodes (TDLNs) to this process in humans is not clear. Here, we studied TDLNs derived from high-grade serous ovarian carcinoma (HGSOC) patients and found that the LNs are disrupted and non-active but rather host a deposit of memory lymphocytes that show tumor-binding potential. Single cell sequencing and multiplex imaging techniques revealed that TDLNs in HGSOC patients lack germinal centres and show limited T and B cell clonal expansion. Thus, the TDLNs may have contributed to the tumor immune response in the past. However, their lack of activity might explain the unsuccessful use of immune checkpoint blockade therapy in this cancer. In future experiments, we aim to uncover the underlying molecular mechanism that imposes the LN dysfunctionality in patients.