Background:
Axillary lymph nodes (ALN) initiate immune responses in breast cancer (BC) but how and when ALN become dysfunctional, facilitating metastasis, is unclear. The fibroblastic reticular cell (FRC) network within ALN provides structural support and mediates immune homeostasis, but we have yet to elucidate whether this network changes during BC progression or not.

Purpose:
We used an unbiased computational approach to quantify features of the immunolabelled FRC network in BC patient-derived ALN. We identified PDGFRβ as a robust, immunomarker for human FRC and used it to quantify how FRC network topology changes during BC progression and after treatment.

Methods:
Formalin-fixed paraffin-embedded ALN (n = 331) from 179 BC patients and 23 benign reactive controls were assessed for FRC network metrics, including lacunarity and branchpoints, alongside de-identified clinico-pathological data. We then integrated this data using multivariate, principal component and survival analyses.

Results:
In node-negative, treatment-naïve triple-negative BC, denser FRC networks in uninvolved nodes significantly improved survival (p = 0.0365). Conversely, similar changes seen in node-positive patients significantly worsened survival (p = 0.0407), regardless of BC subtype or treatment. In metastatic ALN, FRC network disruption grew proportionately to axillary tumour burden, and this significantly correlated with poorer outcomes (p = 0.043). Interestingly, increased FRC alignment within these metastases significantly improved survival (p = 0.0205).

Conclusions:
We have shown that changes in human ALN FRC network topology predict BC prognosis. This could improve how we risk stratify patients in future, and provide a new avenue for mechanistic, translational research.

Background: Gallbladder carcinoma (GBC) remains a highly aggressive malignancy with poor outcomes and limited therapeutic options. The absence of reliable biomarkers for early detection and prognostication further hampers effective management. Tumor budding (TB) and tumor-infiltrating lymphocytes (TILs) have emerged as promising histopathological indicators, reflecting tumor aggressiveness and host immune response in various cancers. However, their significance in GBC remains underexplored.

Methods: This retrospective observational study evaluated the association between TB, TILs, and clinicopathological parameters in histologically confirmed GBC cases that underwent surgical resection. TB and TILs were assessed in 60 patients using standardized protocols, and statistical analyses were performed to determine their correlations with key pathological features.

Results: High TB was significantly associated with advanced tumour stage and higher histological grade, indicating greater tumour aggressiveness. In contrast, high TIL density correlated with earlier stage, lower grade, and the absence of lymphovascular invasion, suggesting a favorable immune response. An inverse relationship was observed between TB and TILs, underscoring the interplay between tumor invasiveness and host immunity.

Conclusion: These findings suggest that TB and TILs serve as complementary prognostic markers in GBC, offering insights into tumor biology and potential avenues for prognostic stratification and targeted therapies. Further studies elucidating the underlying mechanisms of tumor–immune interaction in GBC are warranted to inform clinical translation.