2024

Karjula, Topias; Elomaa, Hanna; Väyrynen, Sara A.; Kuopio, Teijo; Ahtiainen, Maarit; Mustonen, Olli; Puro, Iiris; Niskakangas, Anne; Mecklin, Jukka Pekka; Böhm, Jan; Wirta, Erkki Ville; Seppälä, Toni T.; Sihvo, Eero; Yannopoulos, Fredrik; Helminen, Olli; Väyrynen, Juha P.;

Tumour-associated macrophages (TAMs) express a continuum of phenotypes ranging from an anti-tumoural M1-like phenotype to a pro-tumoural M2-like phenotype. During cancer progression, TAMs may shift to a more M2-like polarisation state, but the role of TAMs in CRC metastases is unclear. We conducted a comprehensive spatial and prognostic analysis of TAMs in CRC pulmonary metastases and corresponding primary tumours using multiplexed immunohistochemistry and machine learning-based image analysis. We obtained data from 106 resected pulmonary metastases and 74 corresponding primary tumours. TAMs in the resected pulmonary metastases were located closer to the cancer cells and presented a more M2-like polarised state in comparison to the primary tumours. Higher stromal M2-like macrophage densities in the invasive margin of pulmonary metastases were associated with worse 5-year overall survival (HR 3.19, 95% CI 1.35–7.55, p = 0.008). The results of this study highlight the value of multiplexed analysis of macrophage polarisation in cancer metastases and might have clinical implications in future cancer therapy.