Supported by various grants and foundations, Angela Riedel's work contributes significantly to the evolving integration of immune-based therapies in cancer treatment.

Her research underscores the importance of immune system modulation in cancer therapy, with lifestyle factors like exercise and diet also playing roles in supporting immune health and potentially reducing metastasis.

Fibroblastic reticulum cells (FRCs) reprogram lymph nodes by releasing cytokines like CCL2 and CCL7, attracting monocytes that become corrupted and inhibit T cell activity, aiding tumor immune evasion.

Preclinical models demonstrate that blocking TLR4 in lymph nodes restores T cell activity and significantly reduces metastasis, especially to the lungs, in TNBC models.

Led by Dr. Angela Riedel at Würzburg University Hospital, the research uncovers how TNBC exploits lymph node environments to evade immune defenses and promote metastasis.

A groundbreaking study published in Immunity reveals a TLR4-dependent fibroblast-monocyte signaling axis in tumor-draining lymph nodes that promotes metastasis in TNBC.

This research highlights the active role of lymph nodes in tumor immune evasion and underscores stromal-immune interactions as critical therapeutic targets, supported by advanced technologies like proteomics and bioinformatics.

Her research has secured several million euros in funding from organizations such as the German Cancer Aid and MMRF, underscoring its significance and potential impact on future cancer therapies.

FRCs are activated via Toll-like receptor 4 (TLR4), a pathway exploited by tumors to dampen immune responses, and blocking TLR4 in mouse models, combined with PD-1 immunotherapy, significantly reduces lung metastases.

Dr. Riedel emphasizes that understanding immune evasion mechanisms in lymph nodes is vital for preventing metastasis and that integrating immune insights into cancer therapy is increasingly crucial.

The research advances understanding of innate immune mechanisms, revealing how TLR4 activation in stromal cells is exploited by tumors to evade immune destruction, highlighting the complex role of immune pathways in cancer progression.

Recent research highlights that immunotherapy, especially when administered near lymph nodes, combined with targeted immune modulation, could be crucial in preventing or reducing metastasis in aggressive breast cancers like triple-negative breast cancer (TNBC).

Clinical analyses of patient lymph node samples confirm immune and stromal alterations similar to those observed in preclinical models, emphasizing the pathway's relevance in human TNBC cases.

The study demonstrates that tumor cells manipulate sentinel lymph nodes before metastasis, creating a premetastatic environment that suppresses immune responses and facilitates cancer spread.

Overall, her work provides a foundation for developing precision immunotherapies aimed at disrupting early metastatic processes and improving outcomes for patients with aggressive breast cancers.

High PD-L1 expression on monocytes in lymph nodes may serve as a biomarker for the effectiveness of PD-1 immunotherapy, even in early disease stages.

PD-L1 expression on monocytes in tumor-draining lymph nodes could help identify patients who are more likely to benefit from PD-1 checkpoint blockade therapies, regardless of tumor PD-L1 status.

Early intervention targeting PD-L1 on monocytes in lymph nodes might improve responses to immunotherapy in breast cancer patients.

Using spatial transcriptomics and single-cell RNA sequencing, the team identified suppressive monocytes and FRCs forming specific niches within lymph nodes that support tumor cell survival and metastasis.

These advanced techniques revealed that clusters of suppressive monocytes are associated with FRCs and T cells within lymph node niches, indicating coordinated immune suppression.

The findings suggest that these immune-suppressive niches within lymph nodes are critical for supporting tumor growth and metastasis.