Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma. (July 2018)

• Record Type: Journal Article
• Authors: Tam, Kenric; Schoppy, David W.; Shin, June Ho; Tay, Joshua K.; Moreno-Nieves, Uriel; Mundy, David C.; Sunwoo, John B.
• Is Part Of: Otolaryngology--head and neck surgery. Volume 159:Number 1(2018)
• Page Start: 76
• Page End: 84
• Publication Date: 2018-07
• Subjects: head and neck squamous cell carcinoma -- CEACAM1 -- NK cells -- immunotherapy -- immuno-oncology; Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599818756627
• Languages: English
• ISSNs: 0194-5998

Abstract

Objective: In conjunction with advances made in cytotoxic chemotherapy, radiation, and surgery, immunotherapy has emerged as a fourth modality of treatment for head and neck squamous cell carcinoma (HNSCC). Understanding the mechanisms by which HNSCC evades immune-mediated control will aid in the development of new therapies to augment an antitumor immune response. Carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) is a cell surface receptor that is expressed on malignant cells and lymphocytes such as natural killer (NK) cells. We sought to determine whether tumor-derived CEACAM1 inhibits NK cell cytotoxicity and whether blockade of CEACAM1 restores antitumor immunity. Study Design: In vitro HNSCC cell line study. Setting: Research laboratory. Subject and Methods: We utilized a real-time cell analyzer to assess NK cell cytotoxicity against an oral squamous cell carcinoma cell line after modulating CEACAM1 expression by cytokines and shRNA knockdown of CEACAM1 expression. Results: NK cells and HNSCC cells both demonstrated cytokine-inducible expression of CEACAM1. Coincubation of NK cells and HNSCC cells resulted in the upregulation of CEACAM1 on the tumor cells. When compared with CEACAM1 - cells, CEACAM1 + tumor cells exhibited increased cell growth and increased size and number of organoids in 3-dimensional culture. Notably, CEACAM1 + HNSCC cells were more resistant to NK cell–mediated killing, but the inhibited expression of CEACAM1 by an shRNA construct restored NK cell cytotoxicity. Conclusion: Together, these data indicate that CEACAM1 acts as an inducible checkpoint molecule, and they support the idea that targeting CEACAM1 could serve as a novel immunotherapy approach in HNSCC.