How Aggressive Breast Cancer Evades Immune Detection Through Lymph Node Changes

Recent research highlights the critical role of lymph nodes in the progression and immune evasion of aggressive breast cancers, such as triple-negative breast cancer (TNBC). In nearly all solid tumors, detecting cancer cells in lymph nodes serves as an important marker for disease advancement, influencing treatment decisions and prognosis. These lymph nodes, which are part of the immune system, act as hubs where immune cells interact to identify and combat pathogens, but cancer cells can manipulate this environment to escape immune detection.

A groundbreaking study conducted by Dr. Angela Riedel and her team at Würzburg University Hospital examined the lymph nodes draining from breast tumors. Notably, they found that even before tumor cells establish themselves in these lymph nodes, the tumor can modify the immune environment—a process known as premetastatic niche formation. This alteration involves fibroblastic reticular cells (FRCs), which normally support lymph node structure and signaling. These cells become activated via Toll-like receptor 4 (TLR4), leading to the release of cytokines like CCL2 and CCL7 that attract monocytes.

Unfortunately, the monocytes within these lymph nodes become 'corrupted,' hampering the activity of T cells that are supposed to fight the cancer. This immune suppression fosters a microenvironment conducive to metastasis, especially in vital organs like the lungs. Using advanced techniques such as spatial transcriptomics and single-cell RNA sequencing, the researchers identified specific niches within lymph nodes where immunosuppressive monocytes, FRCs, and T cells co-localize, supporting tumor growth.

Interestingly, the team demonstrated that blocking TLR4 in mouse models could reverse this immune suppression. When combined with PD1 immunotherapy, this approach restored T-cell activity and significantly reduced lung metastases. These findings were corroborated with patient samples, suggesting that similar processes occur in humans with TNBC. Targeting the tumor-altered lymph node environment thus offers a promising therapeutic avenue.

Furthermore, the study explored the expression of PD-L1 on monocytes within pre-metastatic lymph nodes. Since PD-L1 interacts with PD-1 on T cells to inhibit immune responses, its presence offers an early marker for the effectiveness of PD-1 blockade therapies. The team is now investigating whether therapies can be optimized by administering immunotherapy closer to lymph nodes or combining it with specific chemotherapies. These insights contribute to understanding immune evasion in breast cancer and open pathways for improved treatments that prevent metastasis.

Overall, this research underscores the importance of the immune system’s role in cancer control and demonstrates how tumors can hijack lymph node biology to progress. Interventions targeting these early immune changes could enhance treatment success and patient survival.

Source: https://medicalxpress.com/news/2025-09-lymph-node-reveals-aggressive-breast.html