Thus, assessment of antitumoral effect should consider the quality of immune activation in peritumoral inflammatory cells and their actual proximity to tumour cells.Ĭolorectal cancer (CRC) is the fourth most frequent cause of death among all malignant tumours worldwide. ConclusionĬombined high expression of GZMB and CD68 within 25 μm to tumour cells is an independent prognostic factor in CRC and of superior prognostic value to the well-established CD8 in TNM stage II cancers. p = 0.002) and superior to CD8 in the validation cohort ( p = 0.005 vs. In a multivariate survival analysis, joint analysis of GZMB and CD68 was similarly prognostic to CD8 in the primary cohort ( p = 0.007 vs. Survival analysis showed strongest prognostic effects in the TP25μm zone at the tumour centre for CD8, GZMB and CD68 (all p < 0.001) in the primary cohort and for CD8 ( p = 0.072), GZMB ( p = 0.035) and CD68 ( p = 0.004) in the validation cohort with inferior prognostic effects observed at the tumour invasive margin. In the validation cohort only low GZMB ( p = 0.036) was associated with pT4 stage. ResultsĪssociations notably of advanced TNM stage were observed for low density of CD8 ( p = 0.002), GZMB ( p < 0.001), CD68 ( p = 0.034) and CD163 ( p = 0.011) in the primary cohort. Using digital image analysis, frequency of distinct immune cell types was calculated for tumour proximity (TP) zones with varying radii (10 μm-100 μm) around tumour cells. Immunohistochemical (IHC) staining was performed for CD8, GZMB, CD68 and CD163 on next-generation tissue microarrays (ngTMAs) in a primary cohort ( n = 107) and a TNM stage II validation cohort ( n = 151). We sought to compare the prognostic value of CD8 with downstream indicators of active immune cell function, specifically granzyme B (GZMB) and CD68 in the tumour microenvironment. Previous assessments of peritumoral inflammatory infiltrate in colorectal cancer (CRC) have focused on the role of CD8 + T lymphocytes.
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