Background:
Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, with limited biomarkers available to guide treatment. The tumour microenvironment is highly immunosuppressive, yet the clinical value of immune-based biomarkers remains underexplored. This study aimed to characterise the immune contexture of PDAC using multiplex fluorescence immunohistochemistry to identify prognostic and predictive immune markers.
Methods:
Tumour samples from 27 PDAC patients were analysed using multiplex fluorescence immunohistochemistry to quantify 12 immune and tumour markers. Marker expression was analysed as proportions of total cells and specific immune cell subsets, and these data were correlated with tumour characteristics, patient survival, and adjuvant chemotherapy response.
Results:
Higher CD45+ leukocyte infiltration correlated with increased tumour size (p = 0.022) and perineural invasion (p = 0.002). Higher FOXP3 (p = 0.015), CD11c (p = 0.029), and CD14 (p = 0.045) expression, as well as total T cell infiltration (p = 0.011), also predicted perineural invasion. More advanced tumour grade was associated with lower proportions of cells expressing vimentin (p = 0.018) and PD-L1 (p = 0.020), as well as fewer CD4+ leukocytes (p = 0.031). Considering survival, elevated CD4+ T cell infiltration was significantly associated with longer overall survival (p = 0.038), while increased FOXP3+ regulatory T cells and CD14+ myeloid cells were associated with shorter recurrence-free survival (p = 0.047 and p = 0.016, respectively). Contrary to prior studies, higher densities of CD163+ M2-polarised macrophages correlated with longer recurrence-free survival (p = 0.027). Regarding adjuvant chemotherapy response, greater total CD4+ cell abundance and CD56+ natural killer cell infiltration were associated with favourable responses to cytotoxic therapies (p = 0.020 and p = 0.022, respectively).
Conclusion:
mfIHC-based profiling of PDAC reveals that immune contexture, particularly the balance of helper T cells, regulatory T cells, and myeloid populations, holds strong prognostic and predictive significance. These findings support the development of composite immune scores to stratify patient outcomes and guide therapy decisions. Future research should validate these results in larger cohorts and explore circulating immune correlates to facilitate non-invasive biomarker development.