Immune‐checkpoint molecules on regulatory T‐cells as a potential therapeutic target in head and neck squamous cell cancers. Issue 6 (19th May 2020)

• Record Type: Journal Article
• Authors: Suzuki, Susumu; Ogawa, Tetsuya; Sano, Rui; Takahara, Taishi; Inukai, Daisuke; Akira, Satou; Tsuchida, Hiromi; Yoshikawa, Kazuhiro; Ueda, Ryuzo; Tsuzuki, Toyonori
• Is Part Of: Cancer science. Volume 111:Issue 6(2020)
• Page Start: 1943
• Page End: 1957
• Publication Date: 2020-05-19
• Subjects: head and neck squamous cell carcinoma -- immune checkpoint -- immunotherapy -- regulatory T‐cell -- tumor immune microenvironment; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14422
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Immune‐checkpoint inhibitors improve the survival of head and neck squamous cell carcinoma (HNSCC) patients. Although recent studies have demonstrated that the tumor immune microenvironment (TIME) has critical roles in immunotherapy, the precise mechanisms involved are unclear. Therefore, further investigations of TIME are required for the improvement of immunotherapy. The frequency of effector regulatory T‐cells (eTregs) and the expression of immune‐checkpoint molecules (ICM) on eTregs and conventional T‐cells (Tconvs) both in peripheral blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) from HNSCC patients were analyzed by flow cytometry and their distributions were evaluated by multi‐color immunofluorescence microscopy. High frequency eTreg infiltration into HNSCC tissues was observed and high expressions of CD25, FOXP3, stimulatory‐ICM (4‐1BB, ICOS, OX40 and GITR) and inhibitory‐ICM (programmed cell death‐1 [PD‐1] and cytotoxic T‐lymphocyte‐associated protein‐4 [CTLA‐4]) were found on invasive eTregs. In contrast, the expression of stimulatory‐ICM on Tconvs was low and the expression of inhibitory‐ICM was high. In addition, ICM‐ligands (programmed cell death‐1 [PD‐L1], galectin‐9 and CEACAM‐1) were frequently expressed on cancer cells. PD‐L1 and galectin‐9 were also expressed on macrophages. PD‐1 + T‐cells interacted with PD‐L1 + cancer cells or PD‐L1 + macrophages. This suggested that in TIL, eTregs are highly activated, but Tconvs are exhausted or inactivated by eTregs and immune‐checkpoint systems, and ICM and eTregs are strongly involved in the creation of an immunosuppressive environment in HNSCC tissues. These suggested eTreg targeting drugs are expected to be a combination partner with immune‐checkpoint inhibitors that will improve immunotherapy of HNSCC. Abstract : Frequencies of eTregs populations (CD45RA‐FOXP3hi) in CD4 + T‐cells of PBL and TIL from HNSCC patients were compared. High frequency of eTreg infiltration into HNSCC tissues was revealed. In addition, MFI of CD25 and FOXP3 in eTreg of TIL were higher than in PBL, which indicates that eTreg in TIL are not only highly infiltrated into the tissues but also are highly activated.