Display options
Cite
Soeratram TT, Creemers A, Meijer SL, et al. Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas. J Pathol. 2021;doi: 10.1002/path.5832.
Soeratram, T. T., Creemers, A., Meijer, S. L., de Boer, O. J., Vos, W., Hooijer, G. K., van Berge Henegouwen, M. I., Hulshof, M. C., Bergman, J. J., Lei, M., Bijlsma, M. F., Ylstra, B., van Grieken, N. C., & van Laarhoven, H. W. (2021). Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas. The Journal of pathology, . https://doi.org/10.1002/path.5832
Soeratram, Tanya Td, et al. "Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas." The Journal of pathology vol. (2021). doi: https://doi.org/10.1002/path.5832
Soeratram TT, Creemers A, Meijer SL, de Boer OJ, Vos W, Hooijer GK, van Berge Henegouwen MI, Hulshof MC, Bergman JJ, Lei M, Bijlsma MF, Ylstra B, van Grieken NC, van Laarhoven HW. Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas. J Pathol. 2021 Nov 07; doi: 10.1002/path.5832. Epub 2021 Nov 07. PMID: 34743329.
Copy Download .nbib Format: NLM
Share it on

J Pathol. 2021 Nov 07; doi: 10.1002/path.5832. Epub 2021 Nov 07.

Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas.

The Journal of pathology

Tanya Td Soeratram, Aafke Creemers, Sybren L Meijer, Onno J de Boer, Wim Vos, Gerrit Kj Hooijer, Mark I van Berge Henegouwen, Maarten Ccm Hulshof, Jacques Jghm Bergman, Ming Lei, Maarten F Bijlsma, Bauke Ylstra, Nicole Ct van Grieken, Hanneke Wm van Laarhoven

Affiliations

  1. Department of Pathology, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  2. Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  3. Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  4. Department of Pathology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  5. Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  6. Department of Radiotherapy, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  7. Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  8. Bristol-Myers Squibb, Princeton, NJ, USA.

PMID: 34743329 DOI: 10.1002/path.5832

Abstract

Immunotherapy is a new anti-cancer treatment option, showing promising results in clinical trials. To investigate potential immune biomarkers in esophageal adenocarcinoma (EAC), we explored immune landscape patterns in the tumor microenvironment before and after neoadjuvant chemoradiation (nCRT). Sections from matched pretreatment biopsies and post-nCRT resection specimens (n = 188) were stained for (1) programmed death-ligand 1 (PD-L1, CD274); (2) programmed cell death protein 1 (PD-1, CD279), forkhead box P3 (FOXP3), CD8, pan-cytokeratin multiplex; and (3) an MHC class I, II duplex. The densities of tumor-associated immune cells (TAICs) were calculated using digital image analyses and correlated to histopathological nCRT response [tumor regression grade (TRG)], survival, and post-nCRT immune patterns. PD-L1 positivity defined by a combined positive score of >1 was associated with a better response post-nCRT (TRG 1-3 versus 4, 5, p = 0.010). In addition, high combined mean densities of CD8

© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: PD-L1; biomarker; chemoradiotherapy; digital image analysis; esophageal adenocarcinoma; immunohistochemistry; treatment response; tumor-immune microenvironment; tumor-infiltrating lymphocytes

References

  1. Gebski V, Burmeister B, Smithers BM, et al. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol 2007; 8: 226-234. - PubMed
  2. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol 2011; 12: 681-692. - PubMed
  3. Allum WH, Stenning SP, Bancewicz J, et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol 2009; 27: 5062-5067. - PubMed
  4. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084. - PubMed
  5. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16: 1090-1098. - PubMed
  6. Oppedijk V, van der Gaast A, van Lanschot JJ, et al. Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials. J Clin Oncol 2014; 32: 385-391. - PubMed
  7. Ballman KV. Biomarker: predictive or prognostic? J Clin Oncol 2015; 33: 3968-3971. - PubMed
  8. Califf RM. Biomarker definitions and their applications. Exp Biol Med (Maywood) 2018; 243: 213-221. - PubMed
  9. Creemers A, Ebbing EA, Pelgrim TC, et al. A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas. Sci Rep 2018; 8: 13281. - PubMed
  10. Crumley AB, Going JJ, Hilmy M, et al. Interrelationships between tumor proliferative activity, leucocyte and macrophage infiltration, systemic inflammatory response, and survival in patients selected for potentially curative resection for gastroesophageal cancer. Ann Surg Oncol 2011; 18: 2604-2612. - PubMed
  11. Noble F, Mellows T, McCormick Matthews LH, et al. Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma. Cancer Immunol Immunother 2016; 65: 651-662. - PubMed
  12. Gong J, Chehrazi-Raffle A, Reddi S, et al. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer 2018; 6: 8. - PubMed
  13. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med 2021; 384: 1191-1203. - PubMed
  14. Lazarus J, Maj T, Smith JJ, et al. Spatial and phenotypic immune profiling of metastatic colon cancer. JCI Insight 2018; 3: e121932. - PubMed
  15. Gruosso T, Gigoux M, Manem VSK, et al. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J Clin Invest 2019; 129: 1785-1800. - PubMed
  16. Gong C, Anders RA, Zhu Q, et al. Quantitative characterization of CD8+ T cell clustering and spatial heterogeneity in solid tumors. Front Oncol 2019; 8: 649. - PubMed
  17. Enfield KSS, Martin SD, Marshall EA, et al. Hyperspectral cell sociology reveals spatial tumor-immune cell interactions associated with lung cancer recurrence. J Immunother Cancer 2019; 7: 13. - PubMed
  18. Creemers A, Ebbing EA, Hooijer GKJ, et al. The dynamics of HER2 status in esophageal adenocarcinoma. Oncotarget 2018; 9: 26787-26799. - PubMed
  19. Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994; 73: 2680-2686. - PubMed
  20. Kordes S, van Berge Henegouwen MI, Hulshof MC, et al. Preoperative chemoradiation therapy in combination with panitumumab for patients with resectable esophageal cancer: the PACT study. Int J Radiat Oncol Biol Phys 2014; 90: 190-196. - PubMed
  21. Carlson RV, Boyd KM, Webb DJ. The revision of the Declaration of Helsinki: past, present and future. Br J Clin Pharmacol 2004; 57: 695-713. - PubMed
  22. Bankhead P, Loughrey MB, Fernández JA, et al. QuPath: Open source software for digital pathology image analysis. Sci Rep 2017; 7: 16878. - PubMed
  23. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods 2012; 9: 671-675. - PubMed
  24. van den Ende T, Ter Veer E, Mali RMA, et al. Prognostic and predictive factors for the curative treatment of esophageal and gastric cancer in randomized controlled trials: a systematic review and meta-analysis. Cancers (Basel) 2019; 11: 530. - PubMed
  25. Derks S, Nason KS, Liao X, et al. Epithelial PD-L2 expression marks Barrett's esophagus and esophageal adenocarcinoma. Cancer Immunol Res 2015; 3: 1123-1129. - PubMed
  26. Smyth EC, Gambardella V, Cervantes A, et al. Checkpoint inhibitors for gastroesophageal cancers: dissecting heterogeneity to better understand their role in first-line and adjuvant therapy. Ann Oncol 2021; 32: 590-599. - PubMed
  27. 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
  28. Gajewski TF, Corrales L, Williams J, et al. Cancer immunotherapy targets based on understanding the T cell-inflamed versus non-T cell-inflamed tumor microenvironment. Adv Exp Med Biol 2017; 1036: 19-31. - PubMed
  29. Kelly RJ, Zaidi AH, Smith MA, et al. The dynamic and transient immune microenvironment in locally advanced esophageal adenocarcinoma post chemoradiation. Ann Surg 2018; 268: 992-999. - PubMed
  30. Zingg U, Montani M, Frey DM, et al. Influence of neoadjuvant radio-chemotherapy on tumor-infiltrating lymphocytes in squamous esophageal cancer. Eur J Surg Oncol 2009; 35: 1268-1272. - PubMed
  31. Svensson MC, Lindén A, Nygaard J, et al. T cells, B cells, and PD-L1 expression in esophageal and gastric adenocarcinoma before and after neoadjuvant chemotherapy: relationship with histopathological response and survival. Oncoimmunology 2021; 10: 1921443. - PubMed
  32. van den Ende T, van den Boorn HG, Hoonhout NM, et al. Priming the tumor immune microenvironment with chemo(radio)therapy: a systematic review across tumor types. Biochim Biophys Acta Rev Cancer 2020; 1874: 188386. - PubMed
  33. Bang YJ, Kang YK, Catenacci DV, et al. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer 2019; 22: 828-837. - PubMed
  34. Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390: 2461-2471. - PubMed
  35. Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369: 134-144. - PubMed
  36. Bang YJ, Ruiz EY, Van Cutsem E, et al. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol 2018; 29: 2052-2060. - PubMed
  37. Doi T, Piha-Paul SA, Jalal SI, et al. Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. J Clin Oncol 2018; 36: 61-67. - PubMed
  38. Janjigian YY, Bendell J, Calvo E, et al. CheckMate-032 Study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol 2018; 36: 2836-2844. - PubMed
  39. Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the Phase 2 KEYNOTE-180 Study. JAMA Oncol 2019; 5: 546-550. - PubMed
  40. Shitara K, Özgüroğlu M, Bang YJ, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 2018; 392: 123-133. - PubMed
  41. Bercovici N, Guérin MV, Trautmann A, et al. The remarkable plasticity of macrophages: a chance to fight cancer. Front Immunol 2019; 10: 1563. - PubMed
  42. Derks S, de Klerk LK, Xu X, et al. Characterizing diversity in the tumor-immune microenvironment of distinct subclasses of gastroesophageal adenocarcinomas. Ann Oncol 2020; 31: 1011-1020. - PubMed
  43. Carstens JL, Correa de Sampaio P, Yang D, et al. Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun 2017; 8: 15095. - PubMed
  44. Mazzarella L, Duso BA, Trapani D, et al. The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: a review. Eur J Cancer 2019; 117: 14-31. - PubMed
  45. Zingg U, Montani M, Frey DM, et al. Tumour-infiltrating lymphocytes and survival in patients with adenocarcinoma of the oesophagus. Eur J Surg Oncol 2010; 36: 670-677. - PubMed
  46. Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313: 1960-1964. - PubMed
  47. Kollmann D, Ignatova D, Jedamzik J, et al. PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma. Oncoimmunology 2018; 7: e1435226. - PubMed
  48. van der Werf LR, Dikken JL, van der Willik EM, et al. Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal or junctional cancer: a nationwide study. Eur J Cancer 2018; 91: 76-85. - PubMed
  49. Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods 2012; 9: 676-682. - PubMed
  50. Lowe DG. Distinctive image features from scale-invariant keypoints. Int J Comput Vis 2004; 60: 91-110. - PubMed
  51. Landini G, Martinelli G, Piccinini F. Colour deconvolution: stain unmixing in histological imaging. Bioinformatics 2021; 37: 1485-1487. - PubMed
  52. Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol 2001; 23: 291-299. - PubMed
  53. Legland D, Arganda-Carreras I, Andrey P. MorphoLibJ: integrated library and plugins for mathematical morphology with ImageJ. Bioinformatics 2016; 32: 3532-3534. - PubMed
  54. Yen JC, Chang FJ, Chang S. A new criterion for automatic multilevel thresholding. IEEE Trans Image Process 1995; 4: 370-378. - PubMed
  55. R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, 2019. [Accessed 3 November 2021]. Available from: https://www.R-project.org/. - PubMed

Publication Types

Grant support