CD3-CD8 immune score associated with a clinical score stratifies PDAC prognosis regardless of adjuvant or neoadjuvant chemotherapy

References

• Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, Neale RE, Tempero M, Tuveson DA, Hruban RH, et al. Pancreatic Cancer. Nat Rev Dis Primers. 2016;2(1):16022. doi:10.1038/nrdp.2016.22.
   PubMedGoogle Scholar
• Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic Cancer. Lancet Lond Engl. 2020;395(10242):2008–11. doi:10.1016/S0140-6736(20)30974-0.
   PubMed Web of Science ®Google Scholar
• Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting Cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and Pancreas cancers in the United States. Cancer Res. 2014;74:2913–2921. doi:10.1158/0008-5472.CAN-14-0155.
   PubMed Web of Science ®Google Scholar
• Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, Hruban RH. Recent progress in Pancreatic Cancer. CA Cancer J Clin. 2013;63:318–348. doi:10.3322/caac.21190.
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP. Adjuvant treatment of Pancreatic Cancer. Eur J Cancer. 2011;47(Suppl 3):S378–380. doi:10.1016/S0959-8049(11)70210-6.
   PubMedGoogle Scholar
• Jain T, Dudeja V. The war against pancreatic cancer in 2020 — advances on all fronts. Nat Rev Gastroenterol Hepatol. 2021;18(2):99–100. doi:10.1038/s41575-020-00410-4.
   PubMed Web of Science ®Google Scholar
• Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul J-L, Choné L, Francois E, Artru P, Biagi JJ, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395–2406. doi:10.1056/NEJMoa1809775.
   PubMed Web of Science ®Google Scholar
• Ghaneh P, Palmer D, Cicconi S, Jackson R, Halloran CM, Rawcliffe C, Sripadam R, Mukherjee S, Soonawalla Z, Wadsley J, et al. Immediate surgery compared with Short-Course neoadjuvant Gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable Pancreatic Cancer (ESPAC5): a four-arm, multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8(2):157–168. doi:10.1016/S2468-1253(22)00348-X.
   PubMed Web of Science ®Google Scholar
• Zhang T, Ren Y, Yang P, Wang J, Zhou H. Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma. Cell Death Disease. 2022;13(10):1–11. doi:10.1038/s41419-022-05351-1.
   Web of Science ®Google Scholar
• Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, et al. Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic Pancreatic Adenocarcinoma. J Immunother (1991). 2010;33:828. doi:10.1097/CJI.0b013e3181eec14c.
   PubMed Web of Science ®Google Scholar
• O’Reilly EM, Oh D-Y, Dhani N, Renouf DJ, Lee MA, Sun W, Fisher G, Hezel A, Chang S-C, Vlahovic G, et al. Durvalumab with or without tremelimumab for patients with metastatic Pancreatic Ductal Adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncol. 2019;5(10):1431–1438. doi:10.1001/jamaoncol.2019.1588.
   PubMed Web of Science ®Google Scholar
• Wainberg ZA, Hochster HS, Kim EJ, George B, Kaylan A, Chiorean EG, Waterhouse DM, Guiterrez M, Parikh A, Jain R, et al. Open-label, phase I study of Nivolumab combined with nab-paclitaxel plus gemcitabine in advanced Pancreatic Cancer. Clin Cancer Res. 2020;26:4814–4822. doi:10.1158/1078-0432.CCR-20-0099.
   PubMed Web of Science ®Google Scholar
• Mi H, Sivagnanam S, Betts CB, Liudahl SM, Jaffee EM, Coussens LM, Popel AS. Quantitative Spatial Profiling of Immune Populations in Pancreatic Ductal Adenocarcinoma Reveals Tumor Microenvironment Heterogeneity and Prognostic Biomarkers. Cancer Res. 2022;82:4359–4372. doi:10.1158/0008-5472.CAN-22-1190.
   PubMed Web of Science ®Google Scholar
• Yang S, Liu Q, Liao Q. Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Origin, Polarization, Function, and Reprogramming. Front Cell Dev Biol. 2021;8:607209. doi:10.3389/fcell.2020.607209.
   PubMed Web of Science ®Google Scholar
• Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The Pancreas Cancer microenvironment. Clin Cancer Res Off J Am Assoc Cancer Res. 2012;18(16):4266–4276. doi:10.1158/1078-0432.CCR-11-3114.
   PubMed Web of Science ®Google Scholar
• Fridman WH, Pagès F, Sautès-Fridman C, Galon J. The Immune Contexture in Human Tumours: Impact on Clinical Outcome. Nat Rev Cancer. 2012;12(4):298–306. doi:10.1038/nrc3245.
   PubMed Web of Science ®Google Scholar
• Kiryu S, Ito Z, Suka M, Bito T, Kan S, Uchiyama K, Saruta M, Hata T, Takano Y, Fujioka S, et al. Prognostic value of immune factors in the tumor microenvironment of patients with Pancreatic Ductal Adenocarcinoma. BMC Cancer. 2021;21(1):1197. doi:10.1186/s12885-021-08911-4.
   PubMed Web of Science ®Google Scholar
• Galon J, Pagès F, Marincola FM, Thurin M, Trinchieri G, Fox BA, Gajewski TF, Ascierto PA. The immune score as a New possible approach for the classification of Cancer. J Transl Med. 2012;10(1):1. doi:10.1186/1479-5876-10-1.
   PubMed Web of Science ®Google Scholar
• Pagès F, Mlecnik B, Marliot F, Bindea G, Ou F-S, Bifulco C, Lugli A, Zlobec I, Rau TT, Berger MD, et al. International validation of the consensus Immunoscore for the classification of colon Cancer: a prognostic and accuracy study. Lancet Lond Engl. 2018;391(10135):2128–2139. doi:10.1016/S0140-6736(18)30789-X.
   PubMed Web of Science ®Google Scholar
• Akturk G, Sweeney R, Remark R, Merad M, Gnjatic S. Multiplexed immunohistochemical consecutive staining on single slide (MICSSS): multiplexed chromogenic IHC Assay for high-Dimensional tissue analysis. Methods Mol Biol Clifton NJ. 2020;2055:497–519. doi:10.1007/978-1-4939-9773-2_23.
   PubMedGoogle Scholar
• Bankhead P, Loughrey MB, Fernández JA, Dombrowski Y, McArt DG, Dunne PD, McQuaid S, Gray RT, Murray LJ, Coleman HG, et al. QuPath: Open source software for digital Pathology image analysis. Sci Rep. 2017;7(1):16878. doi:10.1038/s41598-017-17204-5.
   PubMedGoogle Scholar
• Laska E, Meisner M, Wanderling J. A maximally selected test of symmetry about zero. Stat Med. 2012;31:3178–3191. doi:10.1002/sim.5384.
   PubMed Web of Science ®Google Scholar
• Tahkola K, Leppänen J, Ahtiainen M, Väyrynen J, Haapasaari K-M, Karttunen T, Kellokumpu I, Helminen O, Böhm J. Immune Cell Score in Pancreatic Cancer—Comparison of Hotspot and Whole-Section Techniques. Virchows Arch. 2019;474(6):691–699. doi:10.1007/s00428-019-02549-1.
   PubMed Web of Science ®Google Scholar
• Muller M, Haghnejad V, Schaefer M, Gauchotte G, Caron B, Peyrin-Biroulet L, Bronowicki J-P, Neuzillet C, Lopez A. The immune landscape of human Pancreatic Ductal carcinoma: key players, clinical implications, and challenges. Cancers. 2022;14(4):995. doi:10.3390/cancers14040995.
   PubMed Web of Science ®Google Scholar
• Einhaus J, Rochwarger A, Mattern S, Gaudillière B, Schürch CM. High-multiplex tissue imaging in routine Pathology—are We there yet? Virchows Arch. 2023;482(5):801–812. doi:10.1007/s00428-023-03509-6.
   PubMed Web of Science ®Google Scholar
• Liang C-W, Chang R-F, Fang P-W, Chen C-M. Improving algorithm for the alignment of consecutive, whole-slide, immunohistochemical Section images. J Pathol Inform. 2021;12:29. doi:10.4103/jpi.jpi_106_20.
   PubMedGoogle Scholar
• Tahkola K, Mecklin J-P, Wirta E-V, Ahtiainen M, Helminen O, Böhm J, Kellokumpu I. High immune Cell score predicts improved survival in Pancreatic Cancer. Virchows Arch Int J Pathol. 2018;472(4):653–665. doi:10.1007/s00428-018-2297-1.
   PubMed Web of Science ®Google Scholar
• Hu L, Zhu M, Shen Y, Zhong Z, Wu B. The prognostic value of intratumoral and peritumoral tumor-infiltrating FoxP3+Treg cells in of Pancreatic Adenocarcinoma: a meta-analysis. World J Surg Oncol. 2021;19:300. doi:10.1186/s12957-021-02420-1.
   PubMed Web of Science ®Google Scholar
• Wartenberg M, Zlobec I, Perren A, Koelzer VH, Gloor B, Lugli A, Eva K. Accumulation of FOXP3+T-Cells in the tumor microenvironment is associated with an Epithelial-Mesenchymal-transition-type tumor budding phenotype and is an independent prognostic Factor in surgically resected Pancreatic Ductal Adenocarcinoma. Oncotarget. 2015;6(6):4190–4201. doi:10.18632/oncotarget.2775.
   PubMedGoogle Scholar
• Liu L, Zhao G, Wu W, Rong Y, Jin D, Wang D, Lou W, Qin X. Low Intratumoral regulatory T cells and high peritumoral CD8(+) T cells relate to long-term survival in patients with Pancreatic Ductal Adenocarcinoma after Pancreatectomy. Cancer Immunol Immunother CII. 2016;65(1):73–82. doi:10.1007/s00262-015-1775-4.
   PubMed Web of Science ®Google Scholar
• AlMasri S, Zenati M, Hammad A, Nassour I, Liu H, Hogg ME, Zeh HJ, Boone B, Bahary N, Singhi AD, et al. Adaptive dynamic therapy and survivorship for operable Pancreatic Cancer. JAMA Netw Open. 2022;5(6):e2218355. doi:10.1001/jamanetworkopen.2022.18355.
   PubMed Web of Science ®Google Scholar
• Bian J, Almhanna K. Pancreatic Cancer and immune checkpoint inhibitors—still a long way to go. Transl Gastroenterol Hepatol. 2021;6:6. doi:10.21037/tgh.2020.04.03.
   PubMed Web of Science ®Google Scholar