科研之友
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摘要
AimsThis study was designed to test programmed cell death 1 (PD-1) expression of T cells, the hallmark of T cell exhaustion, in different immune-classes' of colorectal carcinoma microenvironments as delineated by unsupervised hierarchical cluster analysis. Methods and resultsA tissue microarray was made with punches from the invasive margins of 40 microsatellite-unstable and 34 microsatellite-stable colorectal carcinomas. Immune cells were phenotyped by CD8, granzyme B, CD4, FoxP3, CD68, S-100, PD-1 and programmed cell death ligand 1 (PD-L1) immunohistochemistry; tumour area per tissue spot was quantified by cytokeratin (CK)18 immunohistochemistry. For each tissue spot, intra-epithelial immune cells were counted and densities of the various immune cells were calculated. Unsupervised hierarchical cluster analysis with these data yielded a group of anergic/immune-naive' microenvironments (47.3%), a group of intermediates' (27.0%) and a group of immunoreactives' (25.7%) in which PD-1 expressing T cells were prominent. Sixteen of 19 tissue spots representing immunoreactive microenvironments derived from microsatellite-unstable tumours and three were from microsatellite-stable tumours. Further phenotyping of intra-epithelial T cells by sequential immunohistochemistry showed frequent granzyme B/CD8 co-expression, whereas PD-1/CD8 co-expression was more variable. Using receiver operating curve (ROC) analysis, assignment to immune classes was seen to be feasible with good sensitivity and specificity by CD8 counts only. ConclusionA subset of colorectal carcinoma microenvironments is distinguished from the rest by an immune cell composition suggestive of active host anti-tumour immune defence, but this appears to be antagonized by a brisk undercurrent of T cell exhaustion. This observation may have implications for selecting colorectal carcinoma patients for immune checkpoint therapy.
- 出版日期2017-9
