Understanding Immune Tolerance of Cancer: Re‐Purposing Insights from Fetal Allografts and Microbes

Abstract

Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non-self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm.

Applications of brain organoids in neurodevelopment and neurological diseases

“…It is known that immunization activities maintain a crucial body defense system and interact with almost all kinds of disorders, such as intracranial infection and neurodegenerative diseases [120][121][122]. Moreover, cancer cells have evolved different mechanisms to simulate peripheral immune tolerance to avoid tumoricidal attack in the process of tumor development [123,124]. Therefore, overcoming this issue will Fig.…”

β3‐Adrenoceptor, a novel player in the round‐trip from neonatal diseases to cancer: Suggestive clues from embryo

“…Immune tolerance is one of the main mechanisms that preserve life and that is shared by cancer and embryo 147,148 . In fact, cancer develops several mechanisms to evade effective immune surveillance and similar mechanisms are used by the fetus to develop in the uterine environment 149,150 .…”

“…Immune tolerance is one of the main mechanisms that preserve life and that is shared by cancer and embryo. 147,148 In fact, cancer develops several mechanisms to evade effective immune surveillance and similar mechanisms are used by the fetus to develop in the uterine environment. 149,150 In this respect, hypoxia is considered one of the most important regulators of cancer immune escape 151 through the activation of Treg cells 152 or the increased resistance of cancer cells to cytotoxic T lymphocytes.…”

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

“…Under normal physiological conditions, immune tolerance is required for self-antigens to prevent autoimmunity (central tolerance), antigens in the gut and liver derived from the microbiome and food (peripheral tolerance), and for non-rejection of the semi-allogenic fetus by the maternal immune system [ 45 ]. Immune tolerance is normally effected by immune editing that occurs centrally in the thymus and bone marrow for T-cells and B-cells, respectively, with deletion of autoreactive lymphocyte clones by apoptosis (negative selection), or induction of anergy.…”