ORIGINAL ARTICLE
Evaluation of spatial PD1 and PD-L1 expression in inflammatory bowel disease samples – a pilot study
1
Department of Methodology, Medical University of Warsaw, Warsaw, Poland
2
Department of Pathology, Professor Witold Orlowski Public Clinical Hospital, Medical Center of Postgraduate Education, Warsaw, Poland
3
Department of Surgery, Professor Witold Orlowski Public Clinical Hospital, Medical Center of Postgraduate Education, Warsaw, Poland
Submission date: 2021-11-01
Final revision date: 2022-01-13
Acceptance date: 2022-03-22
Publication date: 2022-06-29
Pol J Pathol 2022;73(1):50-59
KEYWORDS
TOPICS
ABSTRACT
Alterations of PD1/PD-L1 pathway may be associated with an excessive inflammatory response in the intestinal wall in inflammatory bowel diseases (IBD). To evaluate the expression of PD-1 and PD-L1 in 4 compartments of intestinal wall (mucosa, submucosa, muscularis propria and lymphatic follicles), high-resolution immunohistochemically stained slides were obtained from formalin-fixed paraffin-embedded samples of 10 Crohn’s disease (CD), 9 ulcerative colitis (UC) and 10 unaffected individuals cases. The levels of expression were quantified using the QuPath software.
PD-1 was detected in lymphatic follicles in affected and unaffected tissue samples and in inflammatory infiltration in IBD. There was no difference between groups neither in PD-1 overall expression nor in individual compartments, with the exception of the mucosal expression. It was higher in the mucosa of CD patients comparing to controls, however this difference was marginal (p = 0.0461). PD-L1 was expressed in endothelium and mesenteric nervous plexi, consistently in each group. There were no significant differences in PD-L1 immunoreactivity in context of histologic compartment nor clinical diagnosis. The results suggest that PD-1 and PD-L1 expression in intestinal tissue is heterogeneous in the analysed groups, thus it may be dependent on individual characteristics.
PD-1 was detected in lymphatic follicles in affected and unaffected tissue samples and in inflammatory infiltration in IBD. There was no difference between groups neither in PD-1 overall expression nor in individual compartments, with the exception of the mucosal expression. It was higher in the mucosa of CD patients comparing to controls, however this difference was marginal (p = 0.0461). PD-L1 was expressed in endothelium and mesenteric nervous plexi, consistently in each group. There were no significant differences in PD-L1 immunoreactivity in context of histologic compartment nor clinical diagnosis. The results suggest that PD-1 and PD-L1 expression in intestinal tissue is heterogeneous in the analysed groups, thus it may be dependent on individual characteristics.
REFERENCES (35)
1.
Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol 2014; 20: 91.
2.
Mas-Moya J, Singhi AD. The gross pathology of inflammatory bowel disease. Diagn Histopathol 2015; 21: 261-266.
3.
Loddo I, Romano C. Inflammatory bowel disease: genetics, epigenetics, and pathogenesis. Front Immunol 2015; 6: 551.
4.
Geremia A, Biancheri P, Allan P, et al. Innate and adaptive immunity in inflammatory bowel disease. Autoimmun Rev 2014; 13: 3-10.
5.
Park JH, Peyrin-Biroulet L, Eisenhut M, et al. IBD immunopathogenesis: a comprehensive review of inflammatory molecules. Autoimmun Rev 2017; 16: 416-426.
6.
Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 2018; 18: 153.
7.
Ansari MJI, Salama AD, Chitnis T, et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 2003; 198: 63-69.
8.
Saresella M, Marventano I, Longhi R, et al. CD4+ CD25+ FoxP3+ PD1– regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy. FASEB J 2008; 22: 3500-3508.
9.
Sandigursky S, Silverman GJ, Mor A. Targeting the programmed cell death-1 pathway in rheumatoid arthritis. Autoimmun Rev 2017; 16: 767-773.
10.
Park SJ, Kim J-H, Song M-Y, et al. PD-1 deficiency protects experimental colitis via alteration of gut microbiota. BMB Rep 2017; 50: 578.
11.
Bankhead P, Loughrey MB, Fernández JA, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep 2017; 7: 1-7.
12.
Liu B, Arakawa, Y, Yokogawa R, et al. PD-1/PD-L1 expression in a series of intracranial germinoma and its association with Foxp3+ and CD8+ infiltrating lymphocytes. PloS One 2018; 13: e0194594.
13.
Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann NY Acad Sci 2011; 1217: 45-59.
14.
Maruya M, Kawamoto S, Kato LM, et al. Impaired selection of IgA and intestinal dysbiosis associated with PD-1-deficiency. Gut Microbes 2013; 4: 165-171.
15.
Okazaki T, Okazaki IM, Wang J, et al. PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med 2011; 208: 395-407.
16.
Nishimura H, Nose M, Hiai H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11: 141-151.
17.
Yoshida T, Jiang F, Honjo T, et al. PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice. Proc Natl Acad Sci U S A 2008; 105: 3533-3538.
18.
Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 2001; 291: 319-322.
19.
Okazaki T, Otaka Y, Wang J et al. Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b−/− Pdcd1−/− mice. J Exp Med 2005; 202: 1643-1648.
20.
Troncone G, Gridelli C. The reproducibility of PD-L1 scoring in lung cancer: can the pathologists do better? Transl Lung Cancer Res 2017; 6 (Suppl 1): S74.
21.
Ung C, Kockx M, Waumans Y. Digital pathology in immunooncology – a roadmap for clinical development. Expert Rev Precis Med Drug Dev 2017; 2: 9-19.
22.
Koelzer VH, Sirinukunwattana K, Rittscher J, et al. Precision immunoprofiling by image analysis and artificial intelligence. Virchows Arch 2019; 474: 511-522.
23.
Ahtiainen M, Wirta E-V, Kuopio T, et al. Combined prognostic value of CD274 (PD-L1)/PDCDI (PD-1) expression and immune cell infiltration in colorectal cancer as per mismatch repair status. Mod Pathol 2019; 32: 866.
24.
Sha L, Osinski BL, Ho I, et al. Multi-field-of-view deep learning model predicts nonsmall cell lung cancer programmed death-ligand 1 status from whole-slide hematoxylin and eosin images. J Pathol Inform 2019; 10.
27.
Ohlsson B, Veress B, Lindgren S, et al. Enteric ganglioneuritis and abnormal interstitial cells of Cajal: features of inflammatory bowel disease. Inflamm Bowel Dis 2007; 13: 721-726.
28.
Porcher C, Baldo M, Henry M, et al. Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn’s disease. Am J Gastroenterol 2002; 97: 118-125.
29.
Kanai T, Totsuka T, Uraushihara K, et al. Blockade of B7-H1 Suppresses the Development of Chronic Intestinal Inflammation. J Immunol 2003; 171: 4156-4163.
30.
Nakazawa A, Dotan I, Brimnes J, et al. The Expression and Function of Costimulatory Molecules B7H and B7-H1 on Colonic Epithelial Cells. Gastroenterology 2004; 126: 1347-1357.
31.
Roosenboom B, Horjus Talabur Horje CS, et al. Distribution of Mucosal PD-1 Expressing T Cells in Patients with Colitis of Different Etiologies. Scand J Gastroenterol 2021; 1-9.
32.
Cassol CA, Owen D, Kendra K, et al. Programmed Cell Death-1 (PD-1) and Programmed Death-ligand 1 (PD-L1) Expression in PD-1 Inhibitor-associated Colitis and Its Mimics. Histopathology 2020; 77: 240-249.
33.
Chulkina M, Beswick EJ, Pinchuk IV. Role of PD-L1 in Gut Mucosa Tolerance and Chronic Inflammation. Int J Mol Sci 2020; 21: 9165.
34.
Berger KN, Pu JJ. PD-1 pathway and its clinical application: A 20 year journey after discovery of the complete human PD-1 gene. Gene 2018; 638: 20-25.
35.
Okazaki T, Chikuma S, Iwai Y, et al. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol 2013; 14: 1212-1218.
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| eISSN: | 2084-9869 |
| ISSN: | 1233-9687 |
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