Document Type

Article

Publication Date

2018

Publication Title

Cancers

Volume

10

Issue

3

Pages

69 (19 pages)

DOI

10.3390/cancers10030069

Abstract

Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver. NPS induced specific increases in NKs and NKT-cells expressing CD8 and activation receptors CD314-NKG2D and CD161 (NK1.1) in the TME after treatment, as well as some variable changes in CD4+ and CD8+ effector (Tem) and central memory (Tem) lymphocytes in blood and spleen. After orthotopic challenge, CD8+ T-cells were cytotoxic, inducing apoptosis in N1-S1 cells; additionally, in contrast to post-treatment immune responses, CD4+ and CD8+ memory precursor effector cells (MPECs) and short-lived effector cells (SLECs) were present, while still including CD8+ CD161 NK cells, but not involving CD8+ CD314-NKG2D+ NKs. This immunity was N1-S1-specific and was sustained for at least 8 months. NPS vaccinates rats in vivo against HCC by activating innate and adaptive immune memory mechanisms that prevent HCC recurrence.

Comments

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Original Publication Citation

Lassiter, B. P., Guo, S., & Beebe, S. J. (2018). Nano-pulse stimulation ablates orthotopic rat hepatocellular carcinoma and induces innate and adaptive memory immune mechanisms that prevent recurrence. Cancers,10(3), 69. doi:http://dx.doi.org/10.3390/cancers10030069

ORCID

0000-0002-7280-7888 (Guo), 0000-0002-6075-9452 (Beebe)

Share

COinS