Regorafenib enhances antitumor immune efficacy of anti-PD-L1 immunotherapy on oral squamous cell carcinoma

I. Tsang Chiang, Yuan Hao Lee, Zhao Lin Tan, Fei Ting Hsu*, Hsi Feng Tu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Oral squamous cells carcinoma (OSCC) is the most common oral malignancy that majorly originated from oral cavity. Though the prognostic and predictive value of targeting checkpoint molecules has been reported on OSCC, the treatment efficacy of monotherapy is remaining limited. Several studies suggested that multikinase inhibitors may show potential to facilitate anti-PD-L1-induced anti-tumor immunity. Regorafenib, an oral multikinase inhibitor has been approved by FDA for various types of cancer treatment. Here, we aim to identify whether regorafenib may boost anti-tumor immunity of anti-PD-L1 in MOC1-bearing OSCC animal model. The alteration of immune cells such as M1/M2-like macrophages (MΦ), cytotoxicity T cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) after combination of anti-PD-L1 and regorafenib was validated by flow cytometry and immunohistochemistry staining. The combination index analysis (CI=0.89) supported that regorafenib effectively induce anti-OSCC efficacy of anti-PD-L1. Combination of anti-PD-L1 and regorafenib may not only trigger the polarization of M1-like MΦ (CD11b+CD86+) in mice bone marrow (BM) and spleen (SP), but also induce the accumulation and function of CD8+ T cells in tumor-draining lymph node (TDLN) and tumor. In addition, immunosuppressive related cells (MDSCs and Treg) and factors were all decreased by combination therapy in BM, SP and tumor. In sum, regorafenib may improve anti-OSCC efficacy of anti-PD-L1 through systemically and locally upregulating the immunostimulation immunity and suppressing immunosuppression immunity.

Original languageEnglish
Article number112661
JournalBiomedicine and Pharmacotherapy
StatePublished - Mar 2022


  • Anti-PD-L1
  • Antitumor-induced immunity
  • Oral squamous cells carcinoma
  • Regorafenib


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