Cancer: The Unexpected Role of Lymph Nodes in the Effectiveness of Immunotherapy

Published the 27 July 2026 Updated 24 August 2026

Scientists at the Institut Pasteur have identified a previously unknown mechanism by which antibodies (anti-PD-1), used in immunotherapy against many cancers, amplify the immune response far beyond the tumor itself. By activating specific receptors (FcγR) in the lymph nodes, these antibodies trigger an influx of new circulating antitumor T cells. These results open up concrete avenues for designing more effective immunotherapies.

#Immunothérapie
#Cancer
#Anticorps

“Anti-PD-1” immunotherapies have profoundly changed the management of many cancers. These therapeutic antibodies remove a molecular brake that paralyzes T cells—the immune system cells responsible for destroying cancer cells. By restoring their activity, they enable the body to better fight the tumor.

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What we knew about anti-PD-1 antibodies

It was already known that the lymph nodes near the tumor play a central role in this response: this is where T cells are activated before being sent into battle. But the precise mechanism by which the treatment recruits new circulating T cells to these lymph nodes remained unknown until now.

How does the therapeutic antibody “alert” the lymph node?

Marion Guérin, a researcher in the Dynamics of Immune Responses unit at the Pasteur Institute (formerly led by Philippe Bousso, now by Capucine Grandjean), observed that anti-PD-1 therapy causes rapid swelling of the draining lymph nodes, accompanied by a massive influx of various types of immune cells.

This phenomenon is based on an unexpected interaction. The therapeutic antibody acts as a “bridge” between the T cells to which it binds and other immune cells present in the lymph node, via receptors called FcγR. “Low to moderate activation of these receptors is sufficient to trigger a cascade of signals and the production of type I interferon, signaling molecules that trigger a rapid immune response. Within a few hours, numerous circulating immune cells are drawn to the lymph node, including new T cells capable of joining the fight against the tumor,” explains Marion Guérin.

This mechanism is distinct from the effect previously demonstrated by the team regarding anti-PD-1 on T-cell proliferation within the lymph nodes: the two pathways are complementary.

What are the prospects for treatments? 

These results were confirmed with nivolumab, an anti-PD-1 antibody used in patients, reinforcing the clinical significance of the discovery. They suggest that the design of future immunotherapies could incorporate precise calibration of antibody structure to optimize their interaction with FcγR receptors and maximize T-cell recruitment to draining lymph nodes.

The same mechanism was observed with anti-TIM-3, another therapeutic antibody targeting the immune system, giving it broad applicability beyond the targeting of PD-1 alone.

This work was supported by INSERM, the ARC Foundation, the Ligue contre le Cancer, an Advanced Grant (ENLIGHTEN) from the European Research Council, and the Investissements d'Avenir program managed by the ANR.

Source :

Lymph node fine-tuning FcgR signaling boosts anti-PD-1 therapy, Journal for Immunotherapy of Cancer, June 12, 2026.

Research on the mechanisms of cancer immunotherapies falls under the scientific priority “Pathogenesis of Diseases—Studying the Underlying Mechanisms of Noncommunicable Diseases and Inflammation” of the Pasteur 2030 Strategic Plan.