Neoantigen Quantity and Quality in Relation to Pancreatic Cancer Survival

Iris J M Levink; Lodewijk A A Brosens; Sander S Rensen; Merel R Aberle; Steven S W Olde Damink; Djuna L Cahen; Sonja I Buschow; Gwenny M Fuhler; Maikel P Peppelenbosch; Marco J Bruno

doi:10.3389/fmed.2021.751110

Neoantigen Quantity and Quality in Relation to Pancreatic Cancer Survival

Front Med (Lausanne). 2022 Feb 9:8:751110. doi: 10.3389/fmed.2021.751110. eCollection 2021.

Affiliations

¹ Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
² Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
³ Department of Surgery, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.
⁴ Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany.

Abstract

Introduction: Factors underlying antitumor immunity in pancreatic cancer (PC) are poorly understood. We hypothesized that not neoantigen quantity, but quality, is related to immune cell infiltration and survival.

Methodology: We performed genomic and transcriptomic profiling of paired normal, tumor tissue of 13 patients with PC with distinct survival times. Additionally, neoantigens prediction and immunological profiling were performed.

Results: The proportion of neoantigens with a low similarity-to-self score was higher in short-term survivors (p < 0.0001), while mutational load and burden, similarity-to-known-pathogens, and immunogenicity of neoantigens were not associated with immune cell infiltration or survival.

Discussion: No tumor mutational load or neoantigen quantity, but low similarity-to-self score, was associated with immune cell infiltration and survival.

Keywords: cancer immunity; chromosomal instability disorders; mutation–genetics; neoantigen and shared-antigen vaccine; pancreatic cancer.