Abstract 908
Background
Romidepsin (FK228), a histone deacetylase inhibitor (HDACi), has anti-tumor effects against several types of solid tumors. Studies have suggested that HDACi could upregulate PD-L1 expression in tumor cells, changing the state of anti-tumor immune responses. However, the influence of enhanced PD-L1 expression in tumor cells induced by romidepsin on anti-tumor immune responses are still under debate. So, the purpose of this study was to explore the anti-tumor effects and influence on immune responses of romidepsin in colon cancer.
Methods
The effects of romidepsin on proliferation, cell cycle and apoptosis in the murine colon cancer cell lines CT26 and MC38 were evaluated. PD-L1 expression levels were examined before and after treatment with romidepsin. To analyze the mechanisms through which romidepsin regulates PD-L1 expression, the acetylation of histones H3 and H4 and transcription factor BRD4 was measured. The influence of romidepsin on FOXP3+ regulatory T cells (Tregs), Th1/Th2 balance and IFN-γ+CD8+ T cells was evaluated in a subcutaneous transplanted tumor model and a colitis-associated cancer (CAC) model.
Results
The results indicated that romidepsin inhibited proliferation, induced G0/G1 cell cycle arrest and increased apoptosis in CT26 and MC38 cells. Romidepsin treatment increased PD-L1 expression in CT26 and MC38 cells via increasing the acetylation levels of histones H3 and H4 and regulating the transcription factor BRD4. In subcutaneous transplant tumor mice and CAC mice, romidepsin increased the percentage of FOXP3+ Tregs, decreased the ratio of Th1/Th2 cells and decreased the percentage of IFN-γ+CD8+ T cells in the peripheral blood and the tumor microenvironment. Upon combination with an anti-PD-1 antibody, the anti-tumor effects were enhanced, and the influence on CD4+ and CD8+ T cells was partially reversed.
Conclusions
Although romidepsin had direct anti-tumor effects in murine colon cancer, it increased PD-L1 expression in tumor cells and the percentage of immune-suppressive cells. Combination with anti-PD-1 antibody augmented the anti-tumor effects by reversing the influence of romidepsin on immune cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
National Natural Science Foundation of China.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
5458 - Baseline characteristics from CLARINET FORTE: Evaluating lanreotide autogel (LAN) 120 mg every 14 days in patients with progressive pancreatic or midgut neuroendocrine tumours during a standard first-line LAN regimen.
Presenter: Philippe Ruszniewski
Session: Poster Display session 2
Resources:
Abstract
1234 - Analysis of PD-1/PD-L1 blockade biomarker and immune infiltrates in Gastroenteropancreatic neuroendocrine carcinoma
Presenter: Jia Zhang Xing
Session: Poster Display session 2
Resources:
Abstract
1517 - Diabetes Is Associated With Pancreatic Neuroendocrine Tumors Growth and Metastasis
Presenter: Zhiyao Fan
Session: Poster Display session 2
Resources:
Abstract
2145 - Investigation of the reclassification of G1/G2 pancreatic neuroendocrine neoplasms by WHO 2017 classification
Presenter: Takahiro Yokose
Session: Poster Display session 2
Resources:
Abstract
3134 - Treatment with somatostatin analogues after radiopeptide therapy
Presenter: Daria Handkiewicz Junak
Session: Poster Display session 2
Resources:
Abstract
2191 - Safety and Tolerability of Surufatinib in Western Patients with Solid Tumors
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3253 - The impact of tumour absorbed dosimetry with survival outcomes after peptide receptor radionuclide therapy in metastatic neuroendocrine tumours.
Presenter: Rahul Ladwa
Session: Poster Display session 2
Resources:
Abstract
3581 - Opportunist and Serious Infections in Patients with Neuroendocrine Tumors Treated With Everolimus: A Multicenter Study of Real World Patients
Presenter: Carine Mauro
Session: Poster Display session 2
Resources:
Abstract
5374 - Establishment of Prognostic Nomogram Based on the Metastatic Lymph Nodes Ratio for Patients with Gastric Neuroendocrine Tumour
Presenter: yaobin lin
Session: Poster Display session 2
Resources:
Abstract
3951 - Neutrophil-lymphocyte ratio as an independent predictive factor in Neuroendocrine Neoplasms
Presenter: Sofia Ferreira
Session: Poster Display session 2
Resources:
Abstract