Activation of benign autoimmunity as both tumor and autoimmune disease immunotherapy: a comprehensive review

J Autoimmun. 2014 Nov;54:112-7. doi: 10.1016/j.jaut.2014.05.002. Epub 2014 Jun 10.

Abstract

Here, I consider how benign autoimmunity, the immunological homunculus, can be used to reinstate the healthy regulation of inflammation in both autoimmune diseases and in tumor immunotherapy. Different autoimmune diseases manifest clinically distinct phenotypes, but, in general, they all result from the transition of benign, healthy recognition of key body molecules into a damaging effector reaction. Tumors, in contrast to autoimmune diseases, grow by subverting the immune system into supporting and protecting the growing tumor from immune surveillance. Therefore our therapeutic aim in autoimmune disease is to induce the immune system to down-regulate the specific autoimmune effector reaction that causes the disease; in tumor immunotherapy, on the contrary, we aim to deprive the growing tumor of its illicit activation of immune suppression and to unleash an autoimmune disease targeted to the tumor. The recent success of anti-PD1 and anti-CTLR4 treatments exemplify the reinstatement of tumor autoimmunity subsequent to inhibition of immune suppression. With regard to the therapy of autoimmune diseases, I cite examples of immune system down-regulation of autoimmune diseases by T cell vaccination or HSP60 peptide treatment. Inducing the immune system to regulate itself is safer than global immune suppression and may be more effective in the long run.

Keywords: Autoimmunity; Immune homunculus; Inflammation; Regulation; Tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases* / immunology
  • Autoimmune Diseases* / pathology
  • Autoimmune Diseases* / therapy
  • Autoimmunity*
  • Chaperonin 60* / immunology
  • Chaperonin 60* / pharmacology
  • Humans
  • Mitochondrial Proteins* / immunology
  • Mitochondrial Proteins* / pharmacology
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Peptides* / immunology
  • Peptides* / pharmacology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Vaccination / methods*

Substances

  • Chaperonin 60
  • HSPD1 protein, human
  • Mitochondrial Proteins
  • PDCD1 protein, human
  • Peptides
  • Programmed Cell Death 1 Receptor