ANTXR1 (TEM8) overexpression in gastric adenocarcinoma makes the protein a potential target of immunotherapy

  • Masoud Sotoudeh
  • Ramin Shakeri
  • Sanford M. Dawsey
  • Bahareh Sharififard
  • Naser Ahmadbeigi
  • Mahmood NaderiEmail author
Original Article



Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated.


Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient’s history of neoadjuvant chemotherapy and/or radiotherapy, and the patient’s overall survival.


ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival.


Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.


Chimeric antigen receptor T cell Gastric adenocarcinoma ANTXR1 TEM8 Antigenic targets Immunotherapy 



ANTXR cell adhesion molecule 1

CAR T cell

Chimeric antigen receptor T cells


Erb-b2 receptor tyrosine kinase 2


Kinase insert domain receptor


Metastatic tumor


Non-tumor region


Programmed cell death 1


Patient-derived xenograft


Primary tumor


Tissue microarray


Author contribution

MS, NA, and MN designed the study; MS and BS performed the IHC evaluations; RS performed the statistical data analyses; and MN and SMD prepared the manuscript.


This project was funded by Tehran University of Medical Sciences, Digestive Disease Research Institute grant number 38435-37-02-97.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was performed after the approval of Institutional Review Board of Tehran University of Medical Sciences (approval ID: IR.TUMS.DDRI.REC.1397.007).

Informed consent

Informed consent was obtained from all patients at the time of surgery for the use of their paraffin-embedded tissue blocks in research after finalizing their diagnostic procedure.

Supplementary material

262_2019_2392_MOESM1_ESM.pdf (105.8 mb)
Supplementary material 1 (PDF 108337 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Digestive Diseases Research Center, Digestive Disease Research InstituteTehran University of Medical SciencesTehranIran
  2. 2.Digestive Oncology Research Center, Digestive Disease Research InstituteTehran University of Medical SciencesTehranIran
  3. 3.Metabolic Epidemiology Branch, Division of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesdaUSA
  4. 4.Department of Genetics, Colleague of Science, Kazerun BranchIslamic Azad UniversityKazerunIran
  5. 5.Cell-Based Therapies Research Center, Digestive Disease Research InstituteTehran University of Medical SciencesTehranIran

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