Beschreibung:
<jats:sec><jats:title>Aims</jats:title><jats:p>This study was designed to test programmed cell death 1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐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.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>A 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 <jats:styled-content style="fixed-case">CD</jats:styled-content>8, granzyme B, <jats:styled-content style="fixed-case">CD</jats:styled-content>4, FoxP3, <jats:styled-content style="fixed-case">CD</jats:styled-content>68, S‐100, <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 and programmed cell death ligand 1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1) immunohistochemistry; tumour area per tissue spot was quantified by cytokeratin (<jats:styled-content style="fixed-case">CK</jats:styled-content>)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 <jats:styled-content style="fixed-case">PD</jats:styled-content>‐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/<jats:styled-content style="fixed-case">CD</jats:styled-content>8 co‐expression, whereas <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1/<jats:styled-content style="fixed-case">CD</jats:styled-content>8 co‐expression was more variable. Using receiver operating curve (<jats:styled-content style="fixed-case">ROC</jats:styled-content>) analysis, assignment to immune classes was seen to be feasible with good sensitivity and specificity by <jats:styled-content style="fixed-case">CD</jats:styled-content>8 counts only.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>A 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.</jats:p></jats:sec>