Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
17
12
2021
accepted:
21
07
2022
revised:
01
06
2022
pubmed:
7
9
2022
medline:
28
10
2022
entrez:
6
9
2022
Statut:
ppublish
Résumé
Intraductal papillary neoplasms (IPN) and biliary epithelial neoplasia (BilIN) are well-defined precursor lesions of biliary tract carcinoma (BTC). The aim of this study was to provide a comprehensive characterisation of the inflammatory microenvironment in BTC precursor lesions. Immunohistochemistry was employed to assess tumour-infiltrating immune cells in tissue samples from patients, for whom precursor lesions were identified alongside invasive BTC. The spatiotemporal evolution of the immune microenvironment during IPN-associated carcinogenesis was comprehensively analysed using triplet sample sets of non-neoplastic epithelium, precursor lesion and invasive BTC. Immune-cell dynamics during IPN- and BilIN-associated carcinogenesis were subsequently compared. Stromal CD3 IPN and BilIN are immunologically distinct entities that undergo different immune-cell variations during biliary carcinogenesis. Intraepithelial CD8
Sections du résumé
BACKGROUND
Intraductal papillary neoplasms (IPN) and biliary epithelial neoplasia (BilIN) are well-defined precursor lesions of biliary tract carcinoma (BTC). The aim of this study was to provide a comprehensive characterisation of the inflammatory microenvironment in BTC precursor lesions.
METHODS
Immunohistochemistry was employed to assess tumour-infiltrating immune cells in tissue samples from patients, for whom precursor lesions were identified alongside invasive BTC. The spatiotemporal evolution of the immune microenvironment during IPN-associated carcinogenesis was comprehensively analysed using triplet sample sets of non-neoplastic epithelium, precursor lesion and invasive BTC. Immune-cell dynamics during IPN- and BilIN-associated carcinogenesis were subsequently compared.
RESULTS
Stromal CD3
CONCLUSION
IPN and BilIN are immunologically distinct entities that undergo different immune-cell variations during biliary carcinogenesis. Intraepithelial CD8
Identifiants
pubmed: 36068277
doi: 10.1038/s41416-022-01933-0
pii: 10.1038/s41416-022-01933-0
pmc: PMC9596479
doi:
Substances chimiques
Bile Pigments
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1603-1614Informations de copyright
© 2022. The Author(s).
Références
Brierley JD, Gospodarowicz MK, Wittekind C. (eds). TNM classification of malignant tumours. 8th edn. Hoboken, NJ, USA: Wiley-Blackwell; 2016. p. 272.
Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al. AJCC Cancer Staging Manual. 8th edn. Cham, Switzerland: Springer International Publishing; 2017. p. 1032.
Banales JM, Marin JJG, Lamarca A, Rodrigues PM, Khan SA, Roberts LR, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management. Nat Rev Gastroenterol Hepatol. 2020;17:557–88.
pubmed: 32606456
pmcid: 7447603
doi: 10.1038/s41575-020-0310-z
Kendall T, Verheij J, Gaudio E, Evert M, Guido M, Goeppert B, et al. Anatomical, histomorphological and molecular classification of cholangiocarcinoma. Liver Int. 2019;39:7–18.
pubmed: 30882996
doi: 10.1111/liv.14093
Braconi C, Roessler S, Kruk B, Lammert F, Krawczyk M, Andersen JB. Molecular perturbations in cholangiocarcinoma: Is it time for precision medicine? Liver Int. 2019;39:32–42.
pubmed: 30829432
doi: 10.1111/liv.14085
Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma—evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15:95–111.
pubmed: 28994423
doi: 10.1038/nrclinonc.2017.157
Howlader NNA, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, et al. (eds). SEER cancer statistics review. Bethesda, MD: National Cancer Institute; 1975–2018 [based on November 2020 SEER data submission].
Clements O, Eliahoo J, Kim JU, Taylor-Robinson SD, Khan SA. Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Hepatol. 2020;72:95–103.
pubmed: 31536748
doi: 10.1016/j.jhep.2019.09.007
Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: recent update. World J Gastroenterol. 2017;23:3978–98.
pubmed: 28652652
pmcid: 5473118
doi: 10.3748/wjg.v23.i22.3978
Javle MM, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Waldschmidt DT, et al. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol. 2021;39:265.
doi: 10.1200/JCO.2021.39.3_suppl.265
Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–84.
pubmed: 32203698
pmcid: 8461541
doi: 10.1016/S1470-2045(20)30109-1
Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Final overall survival efficacy results of ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: the phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021;7:1669–77.
Kam AE, Masood A, Shroff RT. Current and emerging therapies for advanced biliary tract cancers. Lancet Gastroenterol Hepatol. 2021;6:956–69.
pubmed: 34626563
doi: 10.1016/S2468-1253(21)00171-0
Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. J Cell Sci. 2012;125:5591–6.
pubmed: 23420197
doi: 10.1242/jcs.116392
Hagerling C, Casbon AJ, Werb Z. Balancing the innate immune system in tumor development. Trends Cell Biol. 2015;25:214–20.
pubmed: 25444276
doi: 10.1016/j.tcb.2014.11.001
Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13:759–71.
pubmed: 24154716
doi: 10.1038/nrc3611
Puré E, Lo A. Can targeting stroma pave the way to enhanced antitumor immunity and immunotherapy of solid tumors? Cancer Immunol Res. 2016;4:269–78.
pubmed: 27036971
pmcid: 5452418
doi: 10.1158/2326-6066.CIR-16-0011
Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity 2019;51:27–41.
pubmed: 31315034
pmcid: 6831096
doi: 10.1016/j.immuni.2019.06.025
Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24:541–50.
pubmed: 29686425
pmcid: 5998822
doi: 10.1038/s41591-018-0014-x
Schlitter AM, Born D, Bettstetter M, Specht K, Kim-Fuchs C, Riener M-O, et al. Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways. Mod Pathol. 2014;27:73–86.
pubmed: 23828315
doi: 10.1038/modpathol.2013.112
Fujikura K, Akita M, Ajiki T, Fukumoto T, Itoh T, Zen Y. Recurrent mutations in APC and CTNNB1 and activated Wnt/β-catenin signaling in intraductal papillary neoplasms of the bile duct: a whole exome sequencing study. Am J Surgical Pathol. 2018;42:1674–85.
doi: 10.1097/PAS.0000000000001155
Goeppert B, Stichel D, Toth R, Fritzsche S, Loeffler MA, Schlitter AM, et al. Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis. Gut. 2021;71:391–401.
WHO. WHO Classification of Tumours Editorial Board: WHO classification of tumours: digestive system tumours. 5th edn. Lyon, France: World Health Organization; 2019.
Torbenson MZY, Yeh MM. Tumors of the liver. Arlington, VA, USA: ARP Press; 2018.
Fukumura Y, Nakanuma Y, Kakuda Y, Takase M, Yao T. Clinicopathological features of intraductal papillary neoplasms of the bile duct: a comparison with intraductal papillary mucinous neoplasm of the pancreas with reference to subtypes. Virchows Arch. 2017;471:65–76.
pubmed: 28550497
doi: 10.1007/s00428-017-2144-9
Goeppert B, Frauenschuh L, Zucknick M, Stenzinger A, Andrulis M, Klauschen F, et al. Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer. Br J Cancer. 2013;109:2665–74.
pubmed: 24136146
pmcid: 3833207
doi: 10.1038/bjc.2013.610
Goeppert B, Frauenschuh L, Zucknick M, Roessler S, Mehrabi A, Hafezi M, et al. Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer. Br J Cancer. 2015;113:1343–9.
pubmed: 26461054
pmcid: 4815783
doi: 10.1038/bjc.2015.337
Nakanuma Y, Uesaka K, Okamura Y, Terada T, Fukumura Y, Kakuda Y, et al. Reappraisal of pathological features of intraductal papillary neoplasm of bile duct with respect to the type 1 and 2 subclassifications. Hum Pathol. 2021;111:21–35.
pubmed: 33508254
doi: 10.1016/j.humpath.2021.01.002
Marks EI, Yee NS. Immunotherapeutic approaches in biliary tract carcinoma: current status and emerging strategies. World J Gastrointest Oncol. 2015;7:338–46.
pubmed: 26600933
pmcid: 4644856
doi: 10.4251/wjgo.v7.i11.338
Jakubowski CD, Azad NS. Immune checkpoint inhibitor therapy in biliary tract cancer (cholangiocarcinoma). Chin Clin Oncol. 2020;9:2.
pubmed: 32008328
doi: 10.21037/cco.2019.12.10
Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep. 2017;7:16878.
pubmed: 29203879
pmcid: 5715110
doi: 10.1038/s41598-017-17204-5
RCoreTeam. R: A Language and Environment for Statistical Computing. Vienna, Austria: https://www.R-project.org ; 2021.
Budczies J, Klauschen F, Sinn BV, Győrffy B, Schmitt WD, Darb-Esfahani S, et al. Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS ONE. 2012;7:e51862.
pubmed: 23251644
pmcid: 3522617
doi: 10.1371/journal.pone.0051862
Young MRI. Redirecting the focus of cancer immunotherapy to premalignant conditions. Cancer Lett. 2017;391:83–8.
pubmed: 28130162
pmcid: 5925415
doi: 10.1016/j.canlet.2017.01.022
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–8.
pubmed: 12407406
doi: 10.1038/ni1102-991
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22:329–60.
pubmed: 15032581
doi: 10.1146/annurev.immunol.22.012703.104803
Luke JJ, Bao R, Sweis RF, Spranger S, Gajewski TF. WNT/β-catenin pathway activation correlates with immune exclusion across human cancers. Clin Cancer Res. 2019;25:3074–83.
pubmed: 30635339
pmcid: 6522301
doi: 10.1158/1078-0432.CCR-18-1942
Seliger B, Massa C. Immune therapy resistance and immune escape of tumors. Cancers. 2021;13:551.
Farhood B, Najafi M, Mortezaee K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol. 2019;234:8509–21.
pubmed: 30520029
doi: 10.1002/jcp.27782
Martínez-Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res. 2015;21:5047–56.
pubmed: 26567364
doi: 10.1158/1078-0432.CCR-15-0685
Dumont N, Liu B, Defilippis RA, Chang H, Rabban JT, Karnezis AN, et al. Breast fibroblasts modulate early dissemination, tumorigenesis, and metastasis through alteration of extracellular matrix characteristics. Neoplasia. 2013;15:249–62.
pubmed: 23479504
pmcid: 3593149
doi: 10.1593/neo.121950
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423–37.
pubmed: 24202395
pmcid: 3954707
doi: 10.1038/nm.3394
Kryza T, Silva LM, Bock N, Fuhrman-Luck RA, Stephens CR, Gao J, et al. Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells. Mol Oncol. 2017;11:1307–29.
pubmed: 28510269
pmcid: 5623815
doi: 10.1002/1878-0261.12075
Mortezaee K. CXCL12/CXCR4 axis in the microenvironment of solid tumors: a critical mediator of metastasis. Life Sci. 2020;249:117534.
pubmed: 32156548
doi: 10.1016/j.lfs.2020.117534
Baker AT, Abuwarwar MH, Poly L, Wilkins S, Fletcher AL. Cancer-associated fibroblasts and T cells: from mechanisms to outcomes. J Immunol. 2021;206:310–20.
pubmed: 33397745
doi: 10.4049/jimmunol.2001203
Kato T, Noma K, Ohara T, Kashima H, Katsura Y, Sato H, et al. Cancer-associated fibroblasts affect intratumoral CD8(+) and FoxP3(+) T cells via IL6 in the tumor microenvironment. Clin Cancer Res. 2018;24:4820–33.
pubmed: 29921731
doi: 10.1158/1078-0432.CCR-18-0205
Lakins MA, Ghorani E, Munir H, Martins CP, Shields JD. Cancer-associated fibroblasts induce antigen-specific deletion of CD8 (+) T Cells to protect tumour cells. Nat Commun. 2018;9:948.
pubmed: 29507342
pmcid: 5838096
doi: 10.1038/s41467-018-03347-0
Ford K, Hanley CJ, Mellone M, Szyndralewiez C, Heitz F, Wiesel P, et al. NOX4 inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumors. Cancer Res. 2020;80:1846–60.
pubmed: 32122909
pmcid: 7611230
doi: 10.1158/0008-5472.CAN-19-3158
Maglietta A, Maglietta R, Staiano T, Bertoni R, Ancona N, Marra G, et al. The immune landscapes of polypoid and nonpolypoid precancerous colorectal lesions. PLoS ONE. 2016;11:e0159373.
pubmed: 27441558
pmcid: 4956166
doi: 10.1371/journal.pone.0159373
Nakanuma Y, Kakuda Y, Uesaka K, Miyata T, Yamamoto Y, Fukumura Y, et al. Characterization of intraductal papillary neoplasm of bile duct with respect to histopathologic similarities to pancreatic intraductal papillary mucinous neoplasm. Hum Pathol. 2016;51:103–13.
pubmed: 27067788
doi: 10.1016/j.humpath.2015.12.022
Roth S, Zamzow K, Gaida MM, Heikenwälder M, Tjaden C, Hinz U, et al. Evolution of the immune landscape during progression of pancreatic intraductal papillary mucinous neoplasms to invasive cancer. EBioMedicine. 2020;54:102714.
pubmed: 32259711
pmcid: 7132171
doi: 10.1016/j.ebiom.2020.102714
Yang C-Y, Huang W-J, Tsai J-H, Cheng A, Chen C-C, Hsu H-P, et al. Targeted next-generation sequencing identifies distinct clinicopathologic and molecular entities of intraductal papillary neoplasms of the bile duct. Mod Pathol. 2019;32:1637–45.
pubmed: 31231124
doi: 10.1038/s41379-019-0306-9
Nakanuma Y, Uesaka K, Kakuda Y, Sugino T, Kubota K, Furukawa T, et al. Intraductal papillary neoplasm of bile duct: updated clinicopathological characteristics and molecular and genetic alterations. J Clin Med. 2020;9:3991.
Yaguchi T, Goto Y, Kido K, Mochimaru H, Sakurai T, Tsukamoto N, et al. Immune suppression and resistance mediated by constitutive activation of Wnt/β-Catenin signaling in human melanoma cells. J Immunol. 2012;189:2110–7.
pubmed: 22815287
doi: 10.4049/jimmunol.1102282
Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124:263–6.
pubmed: 16439202
doi: 10.1016/j.cell.2006.01.007
Jayasingam SD, Citartan M, Thang TH, Mat Zin AA, Ang KC, Ch’ng ES. Evaluating the polarization of tumor-associated macrophages into M1 and M2 phenotypes in human cancer tissue: technicalities and challenges in routine clinical practice. Front Oncol. 2019;9:1512.
pubmed: 32039007
doi: 10.3389/fonc.2019.01512
Thanee M, Loilome W, Techasen A, Namwat N, Boonmars T, Pairojkul C, et al. Quantitative changes in tumor-associated M2 macrophages characterize cholangiocarcinoma and their association with metastasis. Asian Pac J Cancer Prev. 2015;16:3043–50.
pubmed: 25854403
doi: 10.7314/APJCP.2015.16.7.3043
Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18:197–218.
pubmed: 30610226
doi: 10.1038/s41573-018-0007-y
Bonaventura P, Shekarian T, Alcazer V, Valladeau-Guilemond J, Valsesia-Wittmann S, Amigorena S, et al. Cold tumors: a therapeutic challenge for immunotherapy. Front Immunol. 2019;10:168.
pubmed: 30800125
pmcid: 6376112
doi: 10.3389/fimmu.2019.00168
Oh DY, He AR, Qin S, Chen LT, Okusaka T, Vogel A, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI), January 20–22, 2022; San Francisco, CA, USA; Abstract 378.
Tanaka R, Kimura K, Eguchi S, Tauchi J, Shibutani M, Shinkawa H, et al. Preoperative neutrophil-to-lymphocyte ratio predicts tumor-infiltrating CD8(+) T cells in biliary tract cancer. Anticancer Res. 2020;40:2881–7.
pubmed: 32366438
doi: 10.21873/anticanres.14264
Tian L, Ma J, Ma L, Zheng B, Liu L, Song D, et al. PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome. World J Surg Oncol. 2020;18:303.
pubmed: 33228682
pmcid: 7686719
doi: 10.1186/s12957-020-02082-5