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
2840 - Effects of Aerobic and Resistance Exercise on Android:Gynoid Fat Ratio in Breast Cancer Survivors
Presenter: Christina Dieli-Conwright
Session: Poster Display session 2
Resources:
Abstract
869 - Impact of Education for Breast self examination in Rural Indian Women on Early Detection - results of POC study
Presenter: Sneha Parchuri
Session: Poster Display session 2
Resources:
Abstract
1951 - Breast cancer incidence and survival in renal transplant patients: 35-year experience
Presenter: Michalis Kontos
Session: Poster Display session 2
Resources:
Abstract
2017 - The changing landscape of breast cancer incidence after treatment for Hodgkin’s disease
Presenter: Amelia Benjamin
Session: Poster Display session 2
Resources:
Abstract
1780 - Number of deliveries as a prognostic factor in different breast cancer subtypes
Presenter: Anniina Jääskeläinen
Session: Poster Display session 2
Resources:
Abstract
4650 - Effects of supervised and adapted exercise program in the quality of life and strength of breast cancer survivors: MAMA MOVE Gaia trial
Presenter: Ana Joaquim
Session: Poster Display session 2
Resources:
Abstract
4962 - Study On the Socioeconomic and Clinical Factors Affecting the Proportion of Breast Conserving Surgery in Chinese Women Breast Cancer
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract
5451 - Clinical decision making and multidisciplinary team meetings (MDMs) in early breast cancer. Is the agreement between planned and applied therapeutic program?
Presenter: Marco Giavarra
Session: Poster Display session 2
Resources:
Abstract
888 - The value of genetic counselling in breast cancer genetic testing and clinical management
Presenter: Vicki Kiesel
Session: Poster Display session 2
Resources:
Abstract
4005 - Elderly patients in the Japanese Breast Cancer Registry
Presenter: Masataka Sawaki
Session: Poster Display session 2
Resources:
Abstract