Skip to main content

Tumor Immunotherapy of Esophageal and Gastric Cancers

  • Chapter
Cancer Immunology

Abstract

Esophageal and gastric cancers are prevalent and heterogeneous diseases that require patient-specific treatments. Over the past two decades, multidisciplinary approaches have contributed to the development of novel treatments that have significantly improved prognoses. Despite these advancements, survival rates remain low, and novel treatment strategies are required to improve the clinical outcome. The therapeutic potential of cancer immunotherapy has only recently been realized in several cancers, including refractory cancers of the GI tract. Similarly, esophageal and gastric cancers are also amenable to immunotherapy since patients often contain naturally occurring HLA class I-restricted cytotoxic T lymphocytes (CTLs) that specifically target tumor-associated antigens. Prompted by the insights derived from studying these tumor-specific CTLs, therapeutic strategies are currently being developed. This chapter reviews the promising strategies that employ monoclonal antibodies, adoptive cell transfer, and vaccine-based immunotherapy for the treatment of esophageal and gastric cancers. To date, several cancer vaccine trials have been performed in patients with advanced esophageal and gastric cancers. Here, we summarize data from these phase I or phase II clinical trials. For example, a recent phase II trial revealed that vaccination with peptides derived from testicular cancer-specific antigens could improve the prognosis of patients with advanced esophageal cancer. In addition, we describe a novel immunotherapeutic approach, called personalized peptide vaccine (PPV), in which HLA-matched peptides are selected and administered based on preexisting host immunity. Further clinical trials are required to assess the clinical benefits of these immunotherapeutic approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52.

    Article  CAS  PubMed  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.

    Article  CAS  PubMed  Google Scholar 

  3. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  4. Lepage C, Rachet B, Jooste V, Faivre J, Coleman MP. Continuing rapid increase in esophageal adenocarcinoma in England and Wales. Am J Gastroenterol. 2008;103(11):2694–9.

    Article  PubMed  Google Scholar 

  5. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97(2):142–6.

    Article  PubMed  Google Scholar 

  6. Pennathur A, Farkas A, Krasinskas AM, Ferson PF, Gooding WE, Gibson MK, et al. Esophagectomy for T1 esophageal cancer: outcomes in 100 patients and implications for endoscopic therapy. Ann Thorac Surg. 2009;87(4):1048–54.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Polednak AP. Trends in survival for both histologic types of esophageal cancer in US surveillance, epidemiology and end results areas. Int J Cancer. 2003;105(1):98–100.

    Article  CAS  PubMed  Google Scholar 

  8. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36–46.

    Article  CAS  PubMed  Google Scholar 

  9. Enzinger PC, Ilson DH. Irinotecan in esophageal cancer. Oncology. 2000;14(12 Suppl 14):26–30.

    CAS  PubMed  Google Scholar 

  10. Enzinger PC, Ilson DH, Kelsen DP. Chemotherapy in esophageal cancer. Semin Oncol. 1999;26(5 Suppl 15):12–20.

    CAS  PubMed  Google Scholar 

  11. Enzinger PC, Ilson DH, Saltz LB, O’Reilly EM, Kelsen DP. Irinotecan and cisplatin in upper gastrointestinal malignancies. Oncology. 1998;12(8 Suppl 6):110–3.

    CAS  PubMed  Google Scholar 

  12. Homs MY, vd Gaast A, Siersema PD, Steyerberg EW, Kuipers EJ. Chemotherapy for metastatic carcinoma of the esophagus and gastro-esophageal junction. Cochrane Database Syst Rev. 2006(4):CD004063

    Google Scholar 

  13. Shah MA, Ramanathan RK, Ilson DH, Levnor A, D’Adamo D, O’Reilly E, et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2006;24(33):5201–6.

    Article  CAS  PubMed  Google Scholar 

  14. van Meerten E, Eskens FA, van Gameren EC, Doorn L, van der Gaast A. First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study. Br J Cancer. 2007;96(9):1348–52.

    PubMed Central  PubMed  Google Scholar 

  15. Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593–8.

    Article  CAS  PubMed  Google Scholar 

  16. Christie NA, Buenaventura PO, Fernando HC, Nguyen NT, Weigel TL, Ferson PF, et al. Results of expandable metal stents for malignant esophageal obstruction in 100 patients: short-term and long-term follow-up. Ann Thorac Surg. 2001;71(6):1797–801.

    Article  CAS  PubMed  Google Scholar 

  17. Christie NA, Patel AN, Landreneau RJ. Esophageal palliation–photodynamic therapy/stents/brachytherapy. Surg Clin North Am. 2005;85(3):569–82.

    Article  PubMed  Google Scholar 

  18. Lightdale CJ, Heier SK, Marcon NE, McCaughan Jr JS, Gerdes H, Overholt BF, et al. Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial. Gastrointest Endosc. 1995;42(6):507–12.

    Article  CAS  PubMed  Google Scholar 

  19. Litle VR, Luketich JD, Christie NA, Buenaventura PO, Alvelo-Rivera M, McCaughan JS, et al. Photodynamic therapy as palliation for esophageal cancer: experience in 215 patients. Ann Thorac Surg. 2003;76(5):1687–92.

    Article  PubMed  Google Scholar 

  20. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer Statistics, 2009. CA Cancer J Clin. 2009;59(4):225–49.

    Article  PubMed  Google Scholar 

  21. Chang YR, Han DS, Kong SH, Lee HJ, Kim SH, Kim WH, et al. The value of palliative gastrectomy in gastric cancer with distant metastasis. Ann Surg Oncol. 2012;19(4):1231–9.

    Article  PubMed  Google Scholar 

  22. Tokunaga M, Terashima M, Tanizawa Y, Bando E, Kawamura T, Yasui H, et al. Survival benefit of palliative gastrectomy in gastric cancer patients with peritoneal metastasis. World J Surg. 2012;36(11):2637–43.

    Article  PubMed  Google Scholar 

  23. Chen XL, Chen XZ, Yang C, Liao YB, Li H, Wang L, et al. Docetaxel, cisplatin and fluorouracil (DCF) regimen compared with non-taxane-containing palliative chemotherapy for gastric carcinoma: a systematic review and meta-analysis. PLoS One. 2013;8(4):e60320.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012;30(13):1513–8.

    Article  CAS  PubMed  Google Scholar 

  25. Koizumi W. Chemotherapy for advanced gastric cancer: review of global and Japanese status. Gastrointest Cancer Res. 2007;1(5):197–203.

    PubMed Central  PubMed  Google Scholar 

  26. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006;24(31):4991–7.

    Article  CAS  PubMed  Google Scholar 

  27. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.

    Article  CAS  PubMed  Google Scholar 

  28. Sasada T, Suekane S. Variation of tumor-infiltrating lymphocytes in human cancers: controversy on clinical significance. Immunotherapy. 2011;3(10):1235–51.

    Article  CAS  PubMed  Google Scholar 

  29. Senovilla L, Vacchelli E, Galon J, Adjemian S, Eggermont A, Fridman WH, et al. Trial watch: prognostic and predictive value of the immune infiltrate in cancer. OncoImmunology. 2012;1(8):1323–43.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Peng LS, Zhuang Y, Shi Y, Zhao YL, Wang TT, Chen N, et al. Increased tumor-infiltrating CD8(+)Foxp3(+) T lymphocytes are associated with tumor progression in human gastric cancer. Cancer Immunol Immunother. 2012;61(11):2183–92.

    Article  CAS  PubMed  Google Scholar 

  31. Zingg U, Montani M, Frey DM, Dirnhofer S, Esterman AJ, Went P, et al. Tumour-infiltrating lymphocytes and survival in patients with adenocarcinoma of the oesophagus. Eur J Surg Oncol. 2010;36(7):670–7.

    Article  CAS  PubMed  Google Scholar 

  32. Scott AM, Allison JP, Wolchok JD. Monoclonal antibodies in cancer therapy. Cancer Immun. 2012;12:14.

    PubMed Central  PubMed  Google Scholar 

  33. Al-Kasspooles M, Moore JH, Orringer MB, Beer DG. Amplification and over-expression of the EGFR and erbB-2 genes in human esophageal adenocarcinomas. Int J Cancer. 1993;54(2):213–9.

    Article  CAS  PubMed  Google Scholar 

  34. Ross JS, McKenna BJ. The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest. 2001;19(5):554–68.

    Article  CAS  PubMed  Google Scholar 

  35. Brien TP, Odze RD, Sheehan CE, McKenna BJ, Ross JS. HER-2/neu gene amplification by FISH predicts poor survival in Barrett’s esophagus-associated adenocarcinoma. Hum Pathol. 2000;31(1):35–9.

    Article  CAS  PubMed  Google Scholar 

  36. Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51.

    Article  CAS  PubMed  Google Scholar 

  37. Safran H, Dipetrillo T, Akerman P, Ng T, Evans D, Steinhoff M, et al. Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2007;67(2):405–9.

    Article  CAS  PubMed  Google Scholar 

  38. Amedei A, Niccolai E, D’Elios MM. T cells and adoptive immunotherapy: recent developments and future prospects in gastrointestinal oncology. Clin Dev Immunol. 2011;2011:320571.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Kitagawa Y, Ueda M, Ando N, Ozawa S, Shimizu N, Kitajima M. Further evidence for prognostic significance of epidermal growth factor receptor gene amplification in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 1996;2(5):909–14.

    CAS  PubMed  Google Scholar 

  40. Gibault L, Metges JP, Conan-Charlet V, Lozac’h P, Robaszkiewicz M, Bessaguet C, et al. Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer. Br J Cancer. 2005;93(1):107–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Itakura Y, Sasano H, Shiga C, Furukawa Y, Shiga K, Mori S, et al. Epidermal growth factor receptor overexpression in esophageal carcinoma. An immunohistochemical study correlated with clinicopathologic findings and DNA amplification. Cancer. 1994;74(3):795–804.

    Article  CAS  PubMed  Google Scholar 

  42. Ruhstaller T, Pless M, Dietrich D, Kranzbuehler H, von Moos R, Moosmann P, et al. Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II Trial (SAKK 75/06). J Clin Oncol. 2011;29(6):626–31.

    Article  CAS  PubMed  Google Scholar 

  43. Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, et al. A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol. 2011;22(6):1367–73.

    Google Scholar 

  44. Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, et al. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010;5(9):1472–6.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Han SW, Kim HP, Shin JY, Jeong EG, Lee WC, Lee KH, et al. Targeted sequencing of cancer-related genes in colorectal cancer using next-generation sequencing. PLoS One. 2013;8(5):e64271.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Inoue K, Ozeki Y, Suganuma T, Sugiura Y, Tanaka S. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer. 1997;79(2):206–13.

    Article  CAS  PubMed  Google Scholar 

  47. Kitadai Y, Haruma K, Tokutomi T, Tanaka S, Sumii K, Carvalho M, et al. Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas. Clin Cancer Res. 1998;4(9):2195–200.

    CAS  PubMed  Google Scholar 

  48. Kleespies A, Guba M, Jauch KW, Bruns CJ. Vascular endothelial growth factor in esophageal cancer. J Surg Oncol. 2004;87(2):95–104.

    Article  CAS  PubMed  Google Scholar 

  49. Lordick F, Luber B, Lorenzen S, Hegewisch-Becker S, Folprecht G, Woll E, et al. Cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric cancer: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Br J Cancer. 2010;102(3):500–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009;20(10):1667–73.

    Article  CAS  PubMed  Google Scholar 

  51. Pinto C, Di Fabio F, Barone C, Siena S, Falcone A, Cascinu S, et al. Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study). Br J Cancer. 2009;101(8):1261–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C, et al. Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol. 2007;18(3):510–7.

    Article  CAS  PubMed  Google Scholar 

  53. Safran H, Suntharalingam M, Dipetrillo T, Ng T, Doyle LA, Krasna M, et al. Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity. Int J Radiat Oncol Biol Phys. 2008;70(2):391–5.

    Article  CAS  PubMed  Google Scholar 

  54. Maeda K, Chung YS, Takatsuka S, Ogawa Y, Sawada T, Yamashita Y, et al. Tumor angiogenesis as a predictor of recurrence in gastric carcinoma. J Clin Oncol. 1995;13(2):477–81.

    CAS  PubMed  Google Scholar 

  55. Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, et al. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011;29(7):868–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Shih CH, Ozawa S, Ando N, Ueda M, Kitajima M. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res. 2000;6(3):1161–8.

    CAS  PubMed  Google Scholar 

  57. Shimada H, Hoshino T, Okazumi S, Matsubara H, Funami Y, Nabeya Y, et al. Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma. Br J Cancer. 2002;86(4):552–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Earle CC, Kulke MH, et al. Weekly docetaxel, cisplatin, and irinotecan (TPC): results of a multicenter phase II trial in patients with metastatic esophagogastric cancer. Ann Oncol. 2009;20(3):475–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Einzig AI, Neuberg D, Remick SC, Karp DD, O’Dwyer PJ, Stewart JA, et al. Phase II trial of docetaxel (Taxotere) in patients with adenocarcinoma of the upper gastrointestinal tract previously untreated with cytotoxic chemotherapy: the Eastern Cooperative Oncology Group (ECOG) results of protocol E1293. Med Oncol. 1996;13(2):87–93.

    Article  CAS  PubMed  Google Scholar 

  60. El-Rayes BF, Zalupski M, Bekai-Saab T, Heilbrun LK, Hammad N, Patel B, et al. A phase II study of bevacizumab, oxaliplatin, and docetaxel in locally advanced and metastatic gastric and gastroesophageal junction cancers. Ann Oncol. 2010;21(10):1999–2004.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Heath EI, Urba S, Marshall J, Piantadosi S, Forastiere AA. Phase II trial of docetaxel chemotherapy in patients with incurable adenocarcinoma of the esophagus. Invest New Drugs. 2002;20(1):95–9.

    Article  CAS  PubMed  Google Scholar 

  62. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9(4):325–38.

    Article  CAS  PubMed  Google Scholar 

  63. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269–81.

    Article  CAS  PubMed  Google Scholar 

  64. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987;316(15):889–97.

    Google Scholar 

  65. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Vetto JT, et al. A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2. Surgery. 1986;100(2):262–72.

    CAS  PubMed  Google Scholar 

  66. Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, et al. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2010;16(9):2646–55.

    Article  CAS  PubMed  Google Scholar 

  67. Dudley ME, Rosenberg SA. Adoptive cell transfer therapy. Semin Oncol. 2007;34(6):524–31.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Toh U, Yamana H, Sueyoshi S, Tanaka T, Niiya F, Katagiri K, et al. Locoregional cellular immunotherapy for patients with advanced esophageal cancer. Clin Cancer Res. 2000;6(12):4663–73.

    CAS  PubMed  Google Scholar 

  71. Toh U, Sudo T, Kido K, Matono S, Sasahara H, Mine T, et al. Locoregional adoptive immunotherapy resulted in regression in distant metastases of a recurrent esophageal cancer. Int J Clin Oncol. 2002;7(6):372–5.

    Article  PubMed  Google Scholar 

  72. Kim YJ, Lim J, Kang JS, Kim HM, Lee HK, Ryu HS, et al. Adoptive immunotherapy of human gastric cancer with ex vivo expanded T cells. Arch Pharm Res. 2010;33(11):1789–95.

    Article  CAS  PubMed  Google Scholar 

  73. Shi L, Zhou Q, Wu J, Ji M, Li G, Jiang J, et al. Efficacy of adjuvant immunotherapy with cytokine-induced killer cells in patients with locally advanced gastric cancer. Cancer Immunol Immunother. 2012;61(12):2251–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Jiang JT, Shen YP, Wu CP, Zhu YB, Wei WX, Chen LJ, et al. Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients. World J Gastroenterol. 2010;16(48):6155–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Kono K, Takahashi A, Ichihara F, Amemiya H, Iizuka H, Fujii H, et al. Prognostic significance of adoptive immunotherapy with tumor-associated lymphocytes in patients with advanced gastric cancer: a randomized trial. Clin Cancer Res. 2002;8(6):1767–71.

    CAS  PubMed  Google Scholar 

  76. Voskens CJ, Watanabe R, Rollins S, Campana D, Hasumi K, Mann DL. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity. J Exp Clin Cancer Res. 2010;29:134.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–4.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86(24):10024–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Klapper JA, Thomasian AA, Smith DM, Gorgas GC, Wunderlich JR, Smith FO, et al. Single-pass, closed-system rapid expansion of lymphocyte cultures for adoptive cell therapy. J Immunol Methods. 2009;345(1–2):90–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001;61(12):4766–72.

    CAS  PubMed  Google Scholar 

  81. Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Xiangming C, Iwashige H, et al. Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer. Cancer Lett. 2000;159(1):103–8.

    Article  CAS  PubMed  Google Scholar 

  82. Tewari M, Sahai S, Mishra RR, Shukla SK, Shukla HS. Dendritic cell therapy in advanced gastric cancer: a promising new hope? Surg Oncol. 2012;21(3):164–71.

    Article  PubMed  Google Scholar 

  83. Sadanaga N, Nagashima H, Mashino K, Tahara K, Yamaguchi H, Ohta M, et al. Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res. 2001;7(8):2277–84.

    CAS  PubMed  Google Scholar 

  84. Kono K, Takahashi A, Sugai H, Fujii H, Choudhury AR, Kiessling R, et al. Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer. Clin Cancer Res. 2002;8(11):3394–400.

    CAS  PubMed  Google Scholar 

  85. Homma S, Sagawa Y, Ito M, Ohno T, Toda G. Cancer immunotherapy using dendritic/tumour-fusion vaccine induces elevation of serum anti-nuclear antibody with better clinical responses. Clin Exp Immunol. 2006;144(1):41–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Fujiwara S, Wada H, Miyata H, Kawada J, Kawabata R, Nishikawa H, et al. Clinical trial of the intratumoral administration of labeled DC combined with systemic chemotherapy for esophageal cancer. J Immunother. 2012;35(6):513–21.

    Article  CAS  PubMed  Google Scholar 

  87. Finn OJ. Cancer immunology. N Engl J Med. 2008;358(25):2704–15.

    Article  CAS  PubMed  Google Scholar 

  88. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Rosenberg SA. Cell transfer immunotherapy for metastatic solid cancer–what clinicians need to know. Nat Rev Clin Oncol. 2011;8(10):577–85.

    Article  CAS  PubMed  Google Scholar 

  90. Sasada T, Komatsu N, Suekane S, Yamada A, Noguchi M, Itoh K. Overcoming the hurdles of randomised clinical trials of therapeutic cancer vaccines. Eur J Cancer. 2010;46(9):1514–9.

    Article  PubMed  Google Scholar 

  91. Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17):5323–37.

    Article  PubMed  Google Scholar 

  92. Aoki M, Ueda S, Nishikawa H, Kitano S, Hirayama M, Ikeda H, et al. Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432. Vaccine. 2009;27(49):6854–61.

    Article  CAS  PubMed  Google Scholar 

  93. Gilliam AD, Watson SA, Henwood M, McKenzie AJ, Humphreys JE, Elder J, et al. A phase II study of G17DT in gastric carcinoma. Eur J Surg Oncol. 2004;30(5):536–43.

    Article  CAS  PubMed  Google Scholar 

  94. Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, et al. Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma. Cancer Sci. 2010;101(12):2510–7.

    Article  CAS  PubMed  Google Scholar 

  95. Kakimi K, Isobe M, Uenaka A, Wada H, Sato E, Doki Y, et al. A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen. Int J Cancer. 2011;129(12):2836–46.

    Article  CAS  PubMed  Google Scholar 

  96. Kono K, Iinuma H, Akutsu Y, Tanaka H, Hayashi N, Uchikado Y, et al. Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med. 2012;10:141.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Kono K, Mizukami Y, Daigo Y, Takano A, Masuda K, Yoshida K, et al. Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer. Cancer Sci. 2009;100(8):1502–9.

    Article  CAS  PubMed  Google Scholar 

  98. Masuzawa T, Fujiwara Y, Okada K, Nakamura A, Takiguchi S, Nakajima K, et al. Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. Int J Oncol. 2012;41(4):1297–304.

    CAS  PubMed  Google Scholar 

  99. Wada H, Sato E, Uenaka A, Isobe M, Kawabata R, Nakamura Y, et al. Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination. Int J Cancer. 2008;123(10):2362–9.

    Article  CAS  PubMed  Google Scholar 

  100. Noguchi M, Sasada T, Itoh K. Personalized peptide vaccination: a new approach for advanced cancer as therapeutic cancer vaccine. Cancer Immunol Immunother. 2013;62(5):919–29.

    Article  CAS  PubMed  Google Scholar 

  101. Sato Y, Fujiwara T, Mine T, Shomura H, Homma S, Maeda Y, et al. Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients. Cancer Sci. 2007;98(7):1113–9.

    Article  CAS  PubMed  Google Scholar 

  102. Bei R, Scardino A. TAA polyepitope DNA-based vaccines: a potential tool for cancer therapy. J Biomed Biotechnol. 2010;2010:102758.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Chen W, McCluskey J. Immunodominance and immunodomination: critical factors in developing effective CD8+ T-cell-based cancer vaccines. Adv Cancer Res. 2006;95:203–47.

    Article  CAS  PubMed  Google Scholar 

  104. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.

    Article  CAS  PubMed  Google Scholar 

  105. Yewdell JW, Bennink JR. Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol. 1999;17:51–88.

    Article  CAS  PubMed  Google Scholar 

  106. Itoh K, Yamada A. Personalized peptide vaccines: a new therapeutic modality for cancer. Cancer Sci. 2006;97(10):970–6.

    Article  CAS  PubMed  Google Scholar 

  107. Sasada T, Noguchi M, Yamada A, Itoh K. Personalized peptide vaccination: a novel immunotherapeutic approach for advanced cancer. Hum Vaccine Immunother. 2012;8(9):1309–13.

    Article  CAS  Google Scholar 

  108. Sato Y, Shomura H, Maeda Y, Mine T, Une Y, Akasaka Y, et al. Immunological evaluation of peptide vaccination for patients with gastric cancer based on pre-existing cellular response to peptide. Cancer Sci. 2003;94(9):802–8.

    Article  CAS  PubMed  Google Scholar 

  109. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12(4):237–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  110. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8(1):59–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Uhi Toh MD, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Toh, U., Sasada, T., Takahashi, R., Itoh, K., Akagi, Y. (2015). Tumor Immunotherapy of Esophageal and Gastric Cancers. In: Rezaei, N. (eds) Cancer Immunology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46410-6_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-46410-6_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-46409-0

  • Online ISBN: 978-3-662-46410-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics