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

Publisher: Academic Press Country of Publication: England NLM ID: 8812164 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9157 (Electronic) Linking ISSN: 08968411 NLM ISO Abbreviation: J Autoimmun Subsets: MEDLINE

Publication: London : Academic Press
Original Publication: London ; San Diego : Academic Press, c1988-

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

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.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)

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

0 (Chaperonin 60)
0 (HSPD1 protein, human)
0 (Mitochondrial Proteins)
0 (PDCD1 protein, human)
0 (Peptides)
0 (Programmed Cell Death 1 Receptor)

Date Created: 20140614 Date Completed: 20150714 Latest Revision: 20141202

20240628

10.1016/j.jaut.2014.05.002

24924121