High-level STING expression in tumour and inflammatory cells is linked to microsatellite instability and favourable tumour parameters in a cohort of over 1,900 colorectal cancer patients.

Abstract

The stimulator of interferon genes (STING) is expressed on various cell types and tumour entities, where it might enhance antitumoural effects of the immune system and impact tumour angiogenesis. However, the clinical significance of STING expression in tumour cells as compared to tumour-associated inflammatory cells is not fully resolved. To evaluate the clinical significance of STING expression in different cell types of colorectal cancer (CRC), 1,905 patients were analysed by multiplex fluorescence immunohistochemistry in a tissue microarray format in combination with a deep learning algorithm for automated cell detection. High STING expression on tumour was associated with microsatellite instability (MSI, p<0.0001), low tumour stage (pT, p=0.0013), absence of nodal metastasis (pN, p=0.0003) and tumour localisation in the right colon (p<0.0001). Subgroup analysis of tumours with and without MSI did not show associations between STING expression on tumour cells and pT or pN. While the number of CD68^- leukocytes and macrophages was related to MSI, low pT ​and pN0, there were significant associations between a high percentage of STING-positive macrophages and CD68^- leukocytes to low pT (p<0.0001 each) and the absence of metastases for a high percentage of STING-positive macrophages (p=0.0033). In summary, our data show that high STING expression in tumour cells is strongly linked to MSI while STING expression on macrophages and CD68^- leukocytes is tightly linked to the extent of tumour-associated inflammation in CRC.