The immune balance between cancer and autoimmunity
The specific arm of the immune system is comprised from B cells and T cells. T cells include several subtypes among them effector CD4+ T cells that direct and coordinate the biological function of many subtypes of immune cells, effector CD8+ T cells that destroy cancer cells, and viral infected cells, and regulatory CD4+ T cells (Tregs) that control and restrain the activity of effector cells and thereby limit their activities.
The laboratory of Nathan Karin focuses exploring the interplay between subsets of effector and regulatory T cell in the context of cancer and autoimmunity. Our working hypothesis is the interventions towards enhancement of the activities of effector T cells would effectively treats cancer diseases (alone or in combined with immune checkpoint inhibitors), whereas restraining their activity may well treat autoimmune diseases.
The experimental models that are investigated in the lab are: A transgenic cancer model of melanoma (a skin cancer disease), and experimental autoimmune encephalomyelitis (EAE) serving as a model for Multiple Sclerosis (MS), an autoimmune disease of the central nervous system.
In particular the lab currently focuses on how small protein molecules named chemokines, that are associated with cell migration, also direct the lineage development and biological behavior of T cells.
Key recent discoveries of the lab:
1. The discovery of a chemokine that induces regulatory T cells and the discovery of a novel sub-type of these cells, and its amplifications for therapy of cancer and autoimmunity (Barsheshet at al PNAS, 2017)
2. The discovery of the biological mechanism by which one of the major subtypes of myeloid derived suppressor cells is mobilized form the bone marrow to the blood and later to the tumor site to support its development (Hawila et al Cell Reports, 2017)
3. Identification of a novel mechanism by which the immune system restrains cancer growth.
1. Karin N. CXCR3 ligands in cancer and autoimmunity, chemoattraction of effector T cells and beyond. Front Immunol. 2020.
2. Karin N, Razon H. Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. Cytokine. 2018 Feb 12. PubMed PMID: 29449068.
3. Karin N. Chemokines and cancer: new immune checkpoints for cancer therapy. Curr Opin Immunol. 2018 Mar 23;51:140-5. PubMed PMID: 29579623.
4. Karin N. Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity. Front Immunol. 2018;9:623. PubMed PMID: 29651292. Pubmed Central PMCID: 5884937.