Abstract A60: Transcriptional profile of CD56negCD16pos Natural Killer cells within endemic Burkitt lymphoma

Abstract

Abstract Endemic Burkitt lymphoma (eBL), the most common pediatric cancer in equatorial Africa, has long been associated with two etiologic agents: Epstein-Barr virus (EBV) and Plasmodium falciparum malaria. On the other hand, Natural Killer (NK) cells are essential in the clearance of infected cells as well as play a critical role in tumor immunosurveillance. Despite chronic viral infections as HIV, HCV, which have been found to promote the expansion of a CD56 (negative) NK cell subset with impaired effector function, previous cancer studies have been limited to investigations of CD56dimCD16pos NK cells. We previously published that eBL children had significantly more CD56negCD16pos NK cells compared to age-matched healthy children from a low and high malaria transmission area. Here, we characterized this CD56negCD16pos NK subset using histology staining, multicolor flow cytometry, and RNA-sequencing. We found CD56negCD16pos NK cells to be morphologically similar to CD56dimCD16pos NK cells but had higher expression of FCGR3B (CD16b) (p=0.000008) and MPEG1 (Perforin 2) (p=0.0000007), and lower expression of KLRF1 (NKp80), IL18RAP and IL18R1 (IL18 receptor) (p=0.000003, p=0.000003 and p=0.00005, respectively). Phenotypically, CD56negCD16pos NK cells share characteristics of adaptive NK cells; however, they differ from “memory-like” NK cells, with consistent expression of NKG2C/CD57, lower expression of NKp46 and CD160, and higher expression of KIR3DL1 compared to CD56dimCD16pos NK cells. Finally, higher plasma levels of IL-12p70 and IL-2 (known to help NK cell activation and proliferation) and IL-6 and MIP1a were found in healthy compared to eBL children. Together, these findings suggest that the expansion of CD56negCD16pos NK cells could help explain diminished tumor immunosurveillance and might be a mechanism by which EBV-infected cells evades NK-cell mediated immunity. Citation Format: Catherine S. Forconi, Cliff Oduor, John M. Ong’echa, Jeff Bailey, Ann M. Moormann. Transcriptional profile of CD56negCD16pos Natural Killer cells within endemic Burkitt lymphoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A60.