Abstract 1592: Palbociclib enhances anti-PD-L1 therapeutic efficacy in oral squamous cell carcinoma was associated with CXCR4 inactivation
Authors: Wang Chi-Lung , Chiang I-Tsang , Hsu Fei-Ting , Chang Yuan 
Published: July 2021

Abstract
Oral squamous cell carcinoma (OSCC) is a subtype of HNSCC, which was recognized as a common malignant tumor with high mortality in the world. Oral cancer treatment methods include surgery, radiotherapy and adjuvant therapy, but none of these treatment methods can effectively improve the prognosis of oral cancer. The development of OSCC is driven by abnormal cell cycle regulation and immunosuppressive microenvironment. Palbociclib is an inhibitor of CDK4/6, which can trigger cell cycle arrest in cells. Currently, the development of CDK4/6 inhibitors has achieved certain effects on breast cancer patients. However, whether CDK4/6 inhibitors may be used in other cancers, such as OSCC and other cancers still need further discussion and research. In addition, the immunotherapy of programmed death-ligand 1 (PD-L1) inhibitors has recently been explored on many types of cancers. While current data suggested that PD-L1 inhibitor may only be effectively on patient with PD-L1 molecules expression on tumor tissue. Studies have also pointed out that CDK4/6 inhibitor (palbociclib) treatment can induce PD-L1 expression in many different types of cancer and show potential to enhance the efficacy of PD-L1 inhibitors. C-X-C chemokine receptor type 4 was also known to regulate the treatment efficacy via modulating tumor microenvironment (TME). Furthermore, whether CXCR4 inhibition can improve TME and enhance the treatment efficacy of PD-L1 still needs to be investigated. Thus, the goal of this study is to identify whether CDK4/6 can be used to suppress cell proliferation and enhance PD-L1 efficacy via altering TME in OSCC. Here, we used cell viability test, Western blotting, flow cytometry, enzyme-linked immunosorbent assay, and animal experiments to explore the effects of palbociclib combined with PD-L1 inhibitor in OSCC. Our results indicated that palbociclib may suppress cell viability and induce the surface expression of PD-L1 in both human OSCC SAS and mouse OSCC MOC1 cells. Moreover, palbociclib effectively induce extrinsic and intrinsic apoptosis (caspase-3, -8, -9, and mitochondria membrane potential) of OSCC cells. The expression of CXCR4 and its related downstream signaling were decreased by palbociclib. Immune suppressive factors, such as IDO, VEGF, TGF-β was also reduced by palbociclib. Smallest tumor size was also found in palbociclib combined PD-L1 inhibitor groups. Palbociclib may not only suppress tumor proliferation, induce apoptosis and downregulated tumor suppressive factors expression which result in the efficacy induction of anti-PD-L1. In sum, we proposed that palbociclib may enhance treatment efficacy of PD-L1 inhibitor through the inhibition of CXCR4 mediated signaling pathway.
Citation Format: Chi-Lung Wang, I-Tsang Chiang, Fei-Ting Hsu, Yuan Chang. Palbociclib enhances anti-PD-L1 therapeutic efficacy in oral squamous cell carcinoma was associated with CXCR4 inactivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1592.