Study shows how backup lymph nodes help sustain immunotherapy after cancer surgery

Lymph nodes that sit along the drainage pathway from primary tumors are commonly invaded during cancer progression and removed during cancer surgery to prevent cancer from spreading. But these tumor-draining lymph nodes (tdLNs) are also thought to be key sites for anti-cancer immunity.

In a new study led by Lutz Menzel, PhD, and Hengbo Zhou, PhD, former postdoctoral researchers at Mass General Brigham, as well as Timothy Padera, PhD, of the Mass General Brigham Cancer Institute, researchers set out to determine whether, and how, immunotherapy can remain effective after these important immune organs are removed.

The team first conducted a retrospective analysis of patients with advanced melanoma who received surgery and adjuvant immunotherapy. Patients who underwent lymph node dissection remained responsive to immunotherapy, with outcomes similar to those who underwent lymph node biopsy alone. The researchers observed the same pattern in mouse models of melanoma and breast cancer, where immunotherapy remained effective even after tdLN removal.

To understand the mechanism, the team tracked the movement of tumor antigens — proteins on the surfaces of cancer cells that can trigger an immune response — and modeled lymphatic drainage after surgery. They found that tumor antigens were rerouted to more distant, “compensatory,” lymph nodes that took over immune functions normally performed by the removed tdLNs. Evidence of this phenomenon was also seen in patients with head and neck cancer, where favorable responses to immunotherapy were associated with reactive lymph nodes at more distant sites following surgery.

Overall, the findings help explain how the immune system adapts after lymph node removal to maintain anti-cancer responses. They also identify compensatory lymph nodes as promising targets for future immunotherapy strategies.

Published in Immunity on October 1, 2026 | Read the paper: “Distant lymph nodes compensate for resected tumor-draining lymph nodes during cancer immunotherapy”

Summary reviewed by: Timothy Padera, PhD, senior author