In Vitro Evaluation of CMV Specific CD8+T Cells Function in CMV+ Colorectal Cancer Patients Compared to Healthy Controls

  • Mona Shaker Ardakani Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
  • Fatemeh Pak Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran AND Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
  • Parviz Kokhaei Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran AND Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
  • Mohammad Sadegh Fazeli Department of Surgery, Imam Khomeini Complex Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Yadollah Shakiba Regenerative Medicine Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
  • Seyed Morteza Tabatabaei Yazdi Tehran Blood Transfusion Center, Tehran, Iran
  • Ali Abbasian Tehran Blood Transfusion Center, Tehran, Iran
  • Maryam Nourizadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Keywords: Cytomegalovirus, CD107a, Interferon gamma (IFN-γ), Solid tumor

Abstract

The oncogenic role of human cytomegalovirus (HCMV) has been recently shown in different cancers like colorectal cancer (CRC). According to the recent immunotherapy approach to target the CMV-expressing tumor cells, we investigated the CMV peptide-stimulated CD8+T cells functions in CRC patients compared to healthy individuals. All sixteen patients and seven controls were CMV seropositive. Blood samples were obtained from patients without chemotherapy and radiotherapy before surgery. Cytotoxic CD8+ T cells were generated using 14-day culture of PBMCs in the presences of CMV peptide epitopes and rhIL-2. In addition to the supernatant evaluations for TNF-α and IFN-γ, the functionality of CD8+ T cells was examined by detecting CD107a and intracellular IFN-γ using flow cytometry. CMV DNA was detected in tissues by Real Time PCR. CMV DNA was found in 31% of tumor tissues, while it was not seen in the adjacent non-tumor tissues. There was a close association between CMV in tumor tissue and tumor grade. Surface expression of CD107a and intracellular IFN-γ in CMV-stimulated CD8+T cells and the level of IFN-γ production in patient and control groups increased significantly after culture. The number of functions increased in patients (p<0.05) and healthy individuals after culture. Followingstimulation, expressions of CD107a and intracellular IFN-γ were elevated in tumor CMV positive patients while the TNF-α secretion was decreased. In vitro stimulation of PBMC in the presence of CMV peptide epitopes and IL-2 can be an applicable method to generate cytotoxic CD8+ T cells in CRC patients for future T cell therapy.

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Published
2019-08-17
How to Cite
1.
Shaker Ardakani M, Pak F, Kokhaei P, Fazeli MS, Shakiba Y, Tabatabaei Yazdi SM, Abbasian A, Nourizadeh M. In Vitro Evaluation of CMV Specific CD8+T Cells Function in CMV+ Colorectal Cancer Patients Compared to Healthy Controls. Iran J Allergy Asthma Immunol. 18(4):379-392.
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Original Article(s)