Healthy Young Adults have Cellular and Humoral Immune Responses to Multiple Tumor-Associated Antigens

Abstract

Background: Aging-related decline in the immune system is associated with cancer development. Anti-tumor immunity in healthy young adults needs to be elucidated as it is the starting point of the declining course. Here, we aimed to identify antitumor immune responses in healthy young adults. Methods: We analyzed the cellular and humoral immune responses to tumor-associated antigens (TAAs) in nine individuals aged 22–30 (average 23.9) years with HLA-A*24:02. The TAAs included Wilms’ tumor 1 (WT1), New York-esophageal cancer-1 (NY-ESO-1), eukaryotic elongation factor 2 (eEF2), and programmed death ligand 1 (PDL1). We examined TAA antigenic epitope-specific secretion of Th1 (T helper-1)-type cytokines, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and Th2-type cytokine interleukin 10 (IL-10) from peripheral blood mononuclear cells (PBMCs) by enzyme-linked immunospot (ELISPOT) assay. Serum levels of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against these tumor-associated antigen (TAA) epitopes were examined using an enzyme-linked immunosorbent assay (ELISA). Results: The ELISPOT assay revealed that PBMCs from all nine individuals secreted Th1-type cytokines in response to stimulation with TAA antigenic epitopes, showing TAA-specific cellular immune responses. ELISA results revealed that eight of the nine individuals had IgM antibodies against multiple TAA epitopes. IgG antibodies were produced against multiple TAA epitopes in six individuals and against a single TAA epitope in two different individuals. Notably, different modes of cellular and humoral immune response were observed for each specific TAA epitope. Conclusions: Healthy young adults exhibit cellular and humoral immune responses to multiple TAAs. These findings provide an essential piece for understanding antitumor immune surveillance in the context of immune aging.