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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4862 - 5-Fluorouracil induced up-regulation of exosomal PD-L1 causing immunosuppression in gastric cancer patients

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Zhang Min

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

Z. Min1, F. Yibo1, C. Xiaofang1, H. Kezuo1, Q. Xiujuan2

Author affiliations

  • 1 Department Of Medical Oncology, the First Hospital of China Medical University, 110001 - Shenyang/CN
  • 2 Department Of Medical Oncology, the First Hospital of China Medical University, 1100012 - Shenyang/CN
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Resources

Abstract 4862

Background

Although 5-fluorouracil chemotherapy has been thought to directly kill cancer cells and even play an immunostimulatory role, accumulating evidence indicates 5-fluorouracil also damages function of T cells through up-regulating programmed death-1-ligand 1(PD-L1), which is a negative regulator of T cell immune ability. Previous study has shown that PD-L1 has exosomal forms secreted in the microenvironment, except for membrane bound forms and extracellular soluble forms. In addition, exosomal PD-L1 retains stronger immunosuppressive activity. However, whether 5-fluorouracil can change the expression of exosomal PD-L1 and induce immunosuppression is unknown.

Methods

We retrospectively detected exosomal PD-L1, by ELISA, in 17 stage III/IV gastric cancer patients before and after 2,4,6,8 repeated cycles of 5-fluorouracil chemotherapy treatment.

Results

Compared with the expression at baseline, exosomal PD-L1 was up-regulated gradually in the plasma of patients when 2,4,6,8 repeated cycles of 5-fluorouracil were administered, accompanied with the decreased amounts of CD4+ and CD8+ T cells. Mechanistically, 5-fluorouracil up-regulated PD-L1 and exosomal PD-L1 in gastric cancer cell lines. Moreover, exosomal PD-L1 derived from gastric cancer cells induced apoptosis of T cells after 48h treatment, which could be reversed by nivolumab.

Conclusions

5-Fluorouracil up-regulated exosomal PD-L1 which induced apoptosis of T cells and caused immunosuppression in gastric cancer patients.

Clinical trial identification

Legal entity responsible for the study

Academic Group.

Funding

National Natural Science Foundation of China.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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