Abstract 3192: PD-L1 is an independent prognostic marker in Middle Eastern PTC and its expression is upregulated byBRAFV600Emutation

Background: PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. This study was conducted to evaluate the prognostic significance of PD-L1 expression in a large cohort of Middle Eastern PTC patients and to explore correlation of PD-L1 and BRAFV600E mutations in PTC tumors and cell lines. Methods: Immunohistochemistry was performed to assess PD-L1 protein expression in PTC. We further conducted in vitro analysis to investigate the role of PD-L1 in regulating BRAFV600E in PTC cell lines. Results: PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with adverse clinico-pathological parameters such as tall cell variant, extra-thyroidal extension and lymph node metastasis. Importantly, PD-L1 was found to be an independent poorer prognostic marker. We also found PD-L1 to be significantly associated with BRAF mutation and patients with co-existing PD-L1 over-expression and BRAF mutation had a poor disease-free survival compared to patients with BRAF mutation alone. In vitro analysis showed high expression of PD-L1 in BRAF mutated PTC cell lines compared to BRAF wild-type cell line. Inhibition of BRAF using vemurafenib induced PD-L1 expression in BRAF mutated cell lines without affecting cell growth. Knockdown of PD-L1 in BRAF mutated cell lines significantly decreased the cell growth and induced apoptosis. Conclusion: Our data suggests that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as tall cell variant, BRAF mutation positive patients that are unresponsive to standard treatment. Citation Format: Tariq Masoodi, Abdul K. Siraj, Sandeep Kumar Parvathareddy, Poyil Pratheeshkumar, Sasidharan Padmaja Divya, Rafia Begum, Roxanne Diaz, Thangavel Saravanan, Khadija Al-Obaisi, Sarah Siraj, Saud Azam, Zeeshan Qadri, Khawla S. Al-Kuraya. PD-L1 is an independent prognostic marker in Middle Eastern PTC and its expression is upregulated by BRAFV600E mutation [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 3192.