Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Multimodal Anti-tumor Approaches Combined With Immunotherapy To Overcome Tumor Resistance In Esophageal And Gastric Cancer

L. Bolm, L. Käsmann, Annika Paysen, C. Karapetis, D. Rades, U. Wellner, T. Keck, D. Watson, R. Hummel, D. Hussey
Published 2018 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Upper gastrointestinal malignancies are associated with a high disease burden worldwide, and esophageal and gastric cancers represent the most common entities. Given a lack of early characteristic symptoms and potent screening instruments, the majority of patients present with advanced disease at the time of diagnosis. Complete surgical resection is a first-line curative option, and multimodal approaches involving chemotherapy and radiotherapy further improve patient prognosis. However, response to standard adjuvant and neoadjuvant treatments remains low, and new strategies are warranted to increase tumor control rates. Immunotherapy is emerging in various cancer entities and may be successfully combined with standard therapeutic regimens to improve patient outcome. For the purpose of this review we aimed to assess combined approaches of immunotherapy and standard treatment options such as chemotherapy, radiotherapy and surgery. Current trials evaluating multimodal approaches with immunotherapy in esophageal and gastric cancer are evaluated.
This paper references
Adoptive Cell Therapy--Tumor-Infiltrating Lymphocytes, T-Cell Receptors, and Chimeric Antigen Receptors.
S. Feldman (2015)
Monoclonal antibodies in gastrointestinal cancers.
E. Mitchell (1988)
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
Y. Bang (2010)
Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes
J. Zhu (2017)
Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells.
G. Bianchi (2011)
Updates on immunotherapy in non-small cell lung cancer
A. Shimanovsky (2014)
The Complexities of Epidemiology and Prevention of Gastrointestinal Cancers
Saba Haq (2012)
Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries.
María José Domper Arnal (2015)
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.
S. Rosenberg (1987)
Nivolumab: A Review in Advanced Melanoma
L. Scott (2015)
Anti‐gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5
S. Watson (1995)
Advances in targeted therapies and new promising targets in esophageal cancer
A. Belkhiri (2015)
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.
T. Masuzawa (2012)
Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial.
F. Lordick (2013)
Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006)
J. Schachter (2017)
Immunotherapy for oesophagogastric cancer
M. Davidson (2016)
Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.
Jin Li (2016)
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
Phase I clinical trial of vaccination with LY 6 K - derived peptide in patients with advanced
H Ishikawa (2014)
[Treatment of gastric cancer].
G. Zornoza (1982)
Clinical and Immunologic Evaluation of Dendritic Cell–Based Immunotherapy in Combination With Gemcitabine and/or S-1 in Patients With Advanced Pancreatic Carcinoma
Y. Kimura (2012)
The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients
M. Zhang (2016)
[Antibody therapy in cancer].
H. Komatsu (2010)
Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer.
K. Kono (2002)
Immune Checkpoint Inhibitors: New Insights and Current Place in Cancer Therapy
Role of chemoradiotherapy in oesophageal cancer -- adjuvant and neoadjuvant therapy.
S. Gwynne (2014)
Clinical Development of Immune Checkpoint Inhibitors
A. Ito (2015)
Immune Therapy in GI Malignancies: A Review.
Judy Wang (2015)
Immunotherapy in Gastrointestinal Cancers
L. Procaccio (2017)
KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer.
C. Fuchs (2017)
Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial.
J. R. Hecht (2016)
Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A)
Y. Kurokawa (2013)
LBA-009KEYNOTE-059 cohort 3: safety and efficacy of pembrolizumab monotherapy for first-line treatment of patients (pts) with PD-L1-positive advanced gastric/gastroesophageal (G/GEJ) cancer.
V. Catenacci Daniel (2017)
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
Y. Kang (2017)
Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study.
S. Swain (2013)
The epidemiology of esophageal cancer.
A. Russo (1996)
Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study.
P. Thuss-Patience (2017)
Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.
D. Ettinger (2017)
Systematic Review and Meta-analysis of the Influence of HER2 Expression and Amplification in Operable Oesophageal Cancer
D. Chan (2012)
Expression of multidrug resistance-associated proteins and their relation to postoperative individualized chemotherapy in gastric cancer
P. Yu (2014)
Emerging blood-based biomarkers for detection of gastric cancer.
Z. Kalniņa (2015)
Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance
J. Yuan (2016)
Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma.
H. Safran (2007)
Clinicopathological significance of hypoxiainducible factor-1 alpha (HIF-1α) expression in gastric cancer
T Isobe (2013)
Trastuzumab in Combination with FOLFIRI in Patients with Advanced HER2-Positive Gastro-Esophageal Adenocarcinoma: A Retrospective Multicenter AGEO Study
A. Zaanan (2017)
Comparison of the proliferation, cytotoxic activity and cytokine secretion function of cascade primed immune cells and cytokine-induced killer cells in vitro
G. Li (2015)
Programmed Death-1 Ligand-1 (PDL1) Expression Is Associated with the Prognosis of Patients with Stage II/III Gastric Cancer.
Tatsuro Tamura (2015)
Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators
M. Katz (2012)
Treatment for unresectable or metastatic oesophageal cancer: current evidence and trends
P. Rossum (2018)
An open - label , multinational , multicenter study of G 17 DT vaccination combined with cisplatin and 5 - fluorouracil in patients with untreated , advanced gastric or gastroesophageal
JA Ajani
Identification of essential genes for cancer immunotherapy
Shashank J. Patel (2017)
Long-term Outcomes Following Neoadjuvant Chemoradiotherapy for Esophageal Cancer
J. Reynolds (2007)
Pertuzumab in Combination with Trastuzumab Shows Significantly Enhanced Antitumor Activity in HER2-Positive Human Gastric Cancer Xenograft Models
Y. Yamashita-Kashima (2011)
Clinical efficacy of chemotherapy combined with cytokine-induced killer cell treatment after curative resection for gastric cancer patients
Ren Xiu-bao (2012)
Assessment of a HER2 scoring system for gastric cancer: results from a validation study
M. Hofmann (2008)
Efficacy of adjuvant chemotherapy combined with immunotherapy with cytokine-induced killer cells for gastric cancer after d2 gastrectomy.
Y. Chen (2015)
Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial.
T. Kudo (2017)
Correlation between chemosensitivity to anticancer drugs and Bcl-2 expression in gastric cancer.
M. Geng (2013)
Angiogenic and growth factors in gastric cancer.
S. Blank (2015)
Activation of Lysosomal Function During Dendritic Cell Maturation
E. S. Trombetta (2003)
Pancreatic cancer: State‐of‐the‐art care
K. Lillemoe (2000)
Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.
H. Wilke (2014)
Gastric cancer epidemiology and risk factors.
Jon R Kelley (2003)
Induction of CTLs by DCs pulsed with K-ras mutant peptide on the surface of nanoparticles in the treatment of pancreatic cancer.
Guang Tan (2011)
Next generation of cancer immunotherapy calls for combination
P. Cappello (2017)
Autologous tumor lysatepulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients
D Gao (2014)
1200/jco.2016.34.4_suppl.tps185. [Epub ahead of print
YK Kang (2016)
( JCOG 0507 - A )
L Sun (2014)
Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells.
A. Galetto (2001)
Nivolumab for the treatment of bladder cancer
O. Hakenberg (2017)
Subtotal gastrectomy for gastric cancer.
R. Santoro (2014)
3β-Acetyl tormentic acid reverts MRP1/ABCC1 mediated cancer resistance through modulation of intracellular levels of GSH and inhibition of GST activity.
Gleice da Graça Rocha (2014)
HER2 expression in oesophageal carcinoma and Barrett's oesophagus associated adenocarcinoma: An Australian study.
V. Nagaraja (2016)
Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients
H. Iinuma (2013)
Expression of immune checkpoints in T cells of esophageal cancer patients
Jinhua Xie (2016)
Bevacizumab: A Review of Its Use in Advanced Cancer
G. Keating (2014)
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
S. Topalian (2016)
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
M. Valsecchi (2015)
Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).
L. Horn (2017)
Adoptive T‐cell therapy for cancer: The era of engineered T cells
C. Bonini (2015)
In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency.
G. Guo (2008)
Immune responses in patients with esophageal cancer treated with SART1 peptide-pulsed dendritic cell vaccine.
M. Narita (2015)
: The GC 4 study
SA Watson (2006)
An open‐label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5‐fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer : The GC4 study
J. Ajani (2006)
Biologic therapy in esophageal and gastric malignancies: current therapies and future directions.
P. Samson (2017)
Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment.
E. Bollschweiler (2015)
Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
M. Besser (2010)
T Cells and Adoptive Immunotherapy: Recent Developments and Future Prospects in Gastrointestinal Oncology
A. Amedei (2011)
Vaccination of metastatic renal cell carcinoma patients with autologous tumour-derived vitespen vaccine: clinical findings
E. Jonasch (2008)
Adoptive immunotherapy of human gastric cancer with ex vivo expanded T cells
Y. J. Kim (2010)
A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer
Yefei Rong (2011)
Phosphoinositide 3‐kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death
H. Yu (2008)
Multimodality treatment of operable gastric and oesophageal adenocarcinoma: evaluating neoadjuvant, adjuvant and perioperative approaches
M. Davidson (2018)
Effectiveness and safety of chemotherapy combined with cytokine-induced killer cell /dendritic cell-cytokine-induced killer cell therapy for treatment of gastric cancer in China: A systematic review and meta-analysis.
Y. Mu (2016)
Clinical Trial of the Intratumoral Administration of Labeled DC Combined With Systemic Chemotherapy for Esophageal Cancer
Shinichi Fujiwara (2012)
Clinical Roles of Increased Populations of Foxp3+CD4+ T Cells in Peripheral Blood from Advanced Pancreatic Cancer Patients
T. Ikemoto (2006)
Perioperative chemotherapy for resectable gastric cancer: MAGIC and beyond.
A. Choi (2015)
Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer
H. Ishikawa (2013)
Phase I clinical trial of peptide vaccination with URLC10 and VEGFR1 epitope peptides in patients with advanced gastric cancer
Y. Higashihara (2014)
Association of angiogenic factors with prognosis in esophageal cancer
L. Dreikhausen (2015)
Immunotherapy for gastrointestinal malignancies.
Paul G. Toomey (2013)
Global trends in esophageal cancer
G. Malhotra (2017)
KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer.
Y. Bang (2017)
Phase II Trial of Adjuvant Immunotherapy with Autologous Tumor-derived Gp96 Vaccination in Patients with Gastric Cancer
K. Zhang (2017)
Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer.
V. Mazzaferro (2003)
Oesophageal carcinoma
A. Pennathur (2013)
Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP.
L. Sun (2014)
Nanoimmunotherapy: application of nanotechnology for sustained and targeted delivery of antigens to dendritic cells.
Z. Zhang (2012)
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
R. Herbst (2016)
The HER-2/neu Oncogene in Tumors of the Gastrointestinal Tract
J. Ross (2001)
Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study.
A. Ohtsu (2011)
Engineered dendritic cells for gastrointestinal tumor immunotherapy: opportunities in translational research
Arpit Bhargava (2013)
Clinical use of dendritic cells for cancer therapy.
S. Anguille (2014)
Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.
K. Muro (2016)
KEYNOTE-062: Phase III study of pembrolizumab (MK-3475) alone or in combination with chemotherapy versus chemotherapy alone as first-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma.
J. Tabernero (2016)
Pembrolizumab for the treatment of non-small-cell lung cancer.
E. Garon (2015)
BJ: The HER-2/neu oncogene in tumors of the gastrointestinal tract
JS Ross (2001)
Management of Gastric Cancer
S. Mackay (1991)
Potential role of dendritic cell vaccination with MAGE peptides in gastrointestinal carcinomas.
F. Tanaka (2008)
Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial
C. Fuchs (2014)
Current Status and Future Directions of the Immune Checkpoint Inhibitors Ipilimumab, Pembrolizumab, and Nivolumab in Oncology
M. S. Barbee (2015)
Melanoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.
D. Coit (2016)
Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives.
M. Moehler (2016)
Efficacy of dendritic cell-cytokine-induced killer immunotherapy plus intensity-modulated radiation therapy in treating elderly patients with esophageal carcinoma.
L. Yan (2015)
Nivolumab for treating non-small cell lung cancer
N. Guibert (2015)
Expression of epidermal growth factor receptor in esophageal and esophagogastric junction adenocarcinomas
K. Wang (2007)
Review article: the epidemiology and prevention of gastric cancer
K. Fock (2014)
[Gastric cancer].
H. Espejo (1996)
Cancer peptide vaccine to suppress postoperative recurrence in esophageal SCC patients with induction of antigen-specific CD8+ T cell.
T. Yasuda (2017)
Pancreatic cancer: The microenvironment needs attention too!
M. Apte (2015)
Updated results for the advanced esophageal carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab.
T. Doi (2016)

This paper is referenced by
A Scoring Tool to Estimate the Survival of Elderly Patients With Brain Metastases from Esophageal Cancer Receiving Whole-brain Irradiation
Trang Nguyễn (2020)
A Proposed Treatment Approach to Treat Lethal Mutating Cancers
Kevin Roe (2020)
Sub-region based radiomics analysis for survival prediction in oesophageal tumours treated by definitive concurrent chemoradiotherapy
C. Xie (2019)
Hsa_circ_0067997 promotes the progression of gastric cancer by inhibition of miR-515-5p and activation of X chromosome-linked inhibitor of apoptosis (XIAP)
H. Zhang (2019)
SIRT1 in Secretory Organ Cancer
R. Frazzi (2018)
Apigenin Inhibits IL-6 Transcription and Suppresses Esophageal Carcinogenesis
Jian-Ge Qiu (2019)
Imaging biomarkers of contrast-enhanced computed tomography predict survival in oesophageal cancer after definitive concurrent chemoradiotherapy
Chengbing Zeng (2021)
Cancer stem cells and combination therapies to eradicate them.
Q. Tang (2020)
Combining the radiomic features and traditional parameters of 18F-FDG PET with clinical profiles to improve prognostic stratification in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery
Y. Chen* (2019)
Use of immunotherapy in the treatment of gastric cancer
L. Yang (2019)
Semantic Scholar Logo Some data provided by SemanticScholar