Thesis
The roles of Aurora A kinase (AURKA) and WEE1 in regulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC)
Master of Science (M.S.), Drexel University
Aug 2023
DOI:
https://doi.org/10.17918/00001820
Abstract
Head and Neck Squamous Cell Carcinoma (HNSCC) affects the upper aerodigestive tract and is the sixth most common cancer worldwide. It is caused by either Human Papillomavirus (HPV) or tobacco and alcohol consumption. HPV-negative (HPV-) HNSCC has worse prognosis and lower survival rates. AURKA is a crucial cell cycle kinase that regulates mitotic checkpoints, microtubule stability, and chromosome segregation. AURKA overexpression in HPV- HNSCC is common and causes chromosomal instability. WEE1 is another essential kinase that inhibits CDK1, restricting entry to G2/M phase. Combined inhibition of AURKA and WEE1 with two drugs, VIC1911 and adavosertib, enhances antitumor efficacy in HNSCC. The protein PD-L1 is often highly expressed on HNSCC cancer cells. Interaction between PD-L1 and PD-1 on immune cells helps cancer cells evade the immune response. Some published studies suggested AURKA effectors control PD-L1 expression. I investigated whether AURKA and WEE1 influenced PD-L1 expression in two HNSCC cell lines, Cal27 and FaDu. I found that treatment with AURKA and WEE1 inhibitors for24 hours reduced PD-L1 expression in both cell lines, but that extended treatment increased PD-L1 expression in the Cal27 HNSCC cell line. I investigated whether control of PD-L1 expression was at the mRNA or protein level. I found that changes in PD-L1 expression after inhibition of AURKA and WEE1 were linked to altered cell cycle. These data suggesting that use of VIC1911 and adavosertib may influence response to inhibitors of PD-L1, which may alter survival of HPV- HNSCC patients.
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Details
- Title
- The roles of Aurora A kinase (AURKA) and WEE1 in regulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC)
- Creators
- Shabnam Pirestani
- Contributors
- Erica Golemis (Advisor)Todd Strochlic (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- vii, 41 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991021229615004721