Autoimmunity and Cancer-Two Sides of the Same Coin

Abstract

Autoimmune disease results from the immune response against self-antigens, while cancer develops when the immune system does not respond to malignant cells. Thus, for years, autoimmunity and cancer have been considered as two separate fields of research that do not have a lot in common. However, the discovery of immune checkpoints and the development of anti-cancer drugs targeting PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways proved that studying autoimmune diseases can be extremely helpful in the development of novel anti-cancer drugs. Therefore, autoimmunity and cancer seem to be just two sides of the same coin. In the current review, we broadly discuss how various regulatory cell populations, effector molecules, genetic predisposition, and environmental factors contribute to the loss of self-tolerance in autoimmunity or tolerance induction to cancer. With the current paper, we also aim to convince the readers that the pathways involved in cancer and autoimmune disease development consist of similar molecular players working in opposite directions. Therefore, a deep understanding of the two sides of immune tolerance is crucial for the proper designing of novel and selective immunotherapies.

Keywords: autoimmune diseases; cancer immunology; immune tolerance; regulatory cells; tumor microenvironment.

Figure 1

Autoimmunity and cancer as two sides of the same coin. The figure depicts how tuning of immune system regulatory mechanisms can contribute to autoimmunity, health, or cancer development. A decrease in regulatory cell populations like Tregs, Bregs, M2 macrophages, and MDSCs leads to autoimmune disease onset. However, an increase in the same cell subsets is associated with cancer development and progression. Effector molecules involved in immune tolerance induction are downregulated in autoimmunity but overexpressed in cancer. The most important molecules mentioned in the text are listed. AIRE, autoimmune regulator; CTLA-4, cytotoxic T-lymphocyte antigen 4; PD-1, programmed cell death receptor 1; PD-L1, programmed cell death ligand 1; BTLA, B- and T-lymphocyte attenuator; TIM-3, T-cell immunoreceptor with immunoglobulin and ITIM domain; TIGIT, T-cell immunoglobulin and ITIM domain; TGF-beta, transforming growth factor beta; IL, interleukin; ARG-I, arginase I; IDO, indoleamine-pyrrole 2,3-dioxygenase; PNT, peroxynitrite; LAG-3, lymphocyte-activation gene 3 (figure created with BioRender.com).