{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:58:29Z","timestamp":1782255509769,"version":"3.54.5"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of advanced malignancies by boosting immune\u2010mediated destruction of neoplastic cells, but are associated with side effects stemming from generalised immune system activation against normal tissues. Checkpoint ligand expression in non\u2010tumoral cells of tissues affected by immune\u2010related adverse effects has been described in ICI\u2010associated hypophysitis, myocarditis, and acute interstitial nephritis. We aimed to investigate the tissue expression of the immune checkpoint receptor programmed cell death\u20101 (PD\u20101) and its ligand, programmed death\u2010ligand 1 (PD\u2010L1), in PD\u20101 inhibitor\u2010associated colitis (PD1i colitis).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>PD\u20101 and PD\u2010L1 immunohistochemical expression levels were analysed in 15 cases of PD1i colitis and potential mimics\u2014infectious colitis and inflammatory bowel disease (IBD). Increased epithelial expression of PD\u2010L1 was observed in PD1i colitis as compared with normal colon and infectious colitis, but the expression level was lower than that in IBD. Conversely, PD\u20101 expression in inflammatory cells was higher in infectious colitis, intermediate in IBD, and minimal or absent in normal colon and in patients receiving PD\u20101 inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although our results do not justify the use of PD\u2010L1 as a discriminatory marker of PD1i colitis against other entities within the differential diagnosis, they support the concept that PD1i colitis and IBD have similar pathogenetic mechanisms. They also highlight the fact that PD\u2010L1 epithelial overexpression is a commonly used mechanism of the gastrointestinal tract mucosa to protect itself from inflammatory\u2010mediated damage resulting from different aetiologies, which probably underpins the high incidence of gastrointestinal immune\u2010related adverse effects in patients receiving ICI therapies, in whom this mechanism is disrupted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14115","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T20:30:35Z","timestamp":1587069035000},"page":"240-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Programmed cell death\u20101 (PD\u20101) and programmed death\u2010ligand 1 (PD\u2010L1) expression in PD\u20101 inhibitor\u2010associated colitis and its mimics"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-6806","authenticated-orcid":false,"given":"Clarissa A","family":"Cassol","sequence":"first","affiliation":[{"name":"Department of Pathology Division of Medical Oncology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Medical Oncology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Kendra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Division of Medical Oncology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juarez R","family":"Braga","sequence":"additional","affiliation":[{"name":"Institute of Health Policy, Management, and Evaluation University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy L","family":"Frankel","sequence":"additional","affiliation":[{"name":"Department of Pathology Division of Medical Oncology Ohio State University Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A","family":"Arnold","sequence":"additional","affiliation":[{"name":"The University of Colorado Anschutz Medical Campus Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.02.025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12744"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2267-z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13224"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13118"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0904283"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609214"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-019-0363-0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.08.020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008002"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2019.06.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0035-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.162842"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.3.355"},{"key":"e_1_2_8_16_1","unstructured":"CassolC SatoskarA LozanskiGet al.Anti\u2212PD\u20101 immunotherapy may induce interstitial nephritis with increased tubular epithelial expression of PD\u2010L1. 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