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
5612 - Evaluation of germ line mutational status among women with triple-negative breast cancer in Russia
Presenter: Elena Shagimardanova
Session: Poster Display session 2
Resources:
Abstract
4142 - Association of derived neutrophil-to-lymphocyte ratio (dNLR) with pathological complete response (pCR) after neoadjuvant chemotherapy (CT)
Presenter: Alberto Ocaña
Session: Poster Display session 2
Resources:
Abstract
1733 - Competing nomogram for late-period breast cancer-specific death in patients with early-stage hormone receptor-positive breast cancer
Presenter: Jianfei Fu
Session: Poster Display session 2
Resources:
Abstract
1978 - A Nomogram to Predict Pathologic Complete Response of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Based on Simple Blood Indicators
Presenter: Fanrong Zhang
Session: Poster Display session 2
Resources:
Abstract
3062 - Identification of GSTP1 transferred by extracellular vesicles responsible for adriamycin-resistance in breast cancer cells
Presenter: Sujin Yang
Session: Poster Display session 2
Resources:
Abstract
5274 - Expression of X-linked Inhibitor of Apoptosis Protein (XIAP) and its Association with Clinicopathological Parameters in Invasive Breast Cancers
Presenter: Gayathri Devi
Session: Poster Display session 2
Resources:
Abstract
1324 - The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients
Presenter: Soo Youn Bae
Session: Poster Display session 2
Resources:
Abstract
4877 - Correlation of clinical and pathological features with the tumour microenvironment in DCIS. An institutional experience
Presenter: Ann Eapen
Session: Poster Display session 2
Resources:
Abstract
2471 - Correlation between radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer and pathologic complete response and their impact in recurrence-free survival
Presenter: Ariadna Gasol Cudos
Session: Poster Display session 2
Resources:
Abstract
2632 - Ring-like uptake appearance on dedicated breast positron emission tomography before chemotherapy predicts outcome of neoadjuvant chemotherapy in breast cancer
Presenter: Norio Masumoto
Session: Poster Display session 2
Resources:
Abstract