From Cancer to Immune-Mediated Diseases and Tolerance Induction: Lessons Learned From Immune Oncology and Classical Anti-cancer Treatment

Abstract

Success in cancer treatment over the last four decades has ranged from improvements in classical drug therapy to immune oncology. Anti-cancer drugs have also often proven beneficial for the treatment of inflammatory and autoimmune diseases. In this review, we report on challenging examples that bridge between treatment of cancer and immune-mediated diseases, addressing mechanisms and experimental models as well as clinical investigations. Patient-derived tumor xenograft (PDX) (humanized) mouse models represent useful tools for preclinical evaluation of new therapies and biomarker identification. However, new developments using human ex vivo approaches modeling cancer, for example in microfluidic human organs-on-chips, promise to identify key molecular, cellular and immunological features of human cancer progression in a fully human setting. Classical drugs which bridge the gap, for instance, include cytotoxic drugs, proteasome inhibitors, PI3K/mTOR inhibitors and metabolic inhibitors. Biologicals developed for cancer therapy have also shown efficacy in the treatment of autoimmune diseases. In immune oncology, redirected chimeric antigen receptor (CAR) T cells have achieved spectacular remissions in refractory B cell leukemia and lymphoma and are currently under development for tolerance induction using cell-based therapies such as CAR Tregs or NK cells. Finally, a brief outline will be given of the lessons learned from bridging cancer and autoimmune diseases as well as tolerance induction.

Association between Circulating T Cells and the Gut Microbiome in Healthy Individuals: Findings from a Pilot Study

“…The dysregulation or excessive activation of CD8+ T cells can lead to various immune-mediated diseases, including autoimmune disorders and chronic inflammatory conditions. For instance, the dysregulation of CD8+ T cell activation can contribute to the development of autoimmune diseases such as autoinflammatory diseases and chronic autoimmune conditions, leading to increased morbidity and mortality [29,30]. The balance of T cell activation is crucial, as it can result in either tolerogenic or proinflammatory outcomes, impacting the immune response and the development of immune-mediated diseases.…”

An updated overview of the application of CAR‐T cell therapy in neurological diseases

“…20 It would be preferable to proceed with extra caution when developing their specific CAR-Treg therapy because demyelinating disorders are not immediately fatal, unlike malignancies, life-threatening conditions treated with available CAR-T cell treatments. 100,101…”

“…Additionally, myelin‐dependent immune system suppression may make patients more vulnerable to infections and illnesses such as nerve sheath tumors 20 . It would be preferable to proceed with extra caution when developing their specific CAR‐Treg therapy because demyelinating disorders are not immediately fatal, unlike malignancies, life‐threatening conditions treated with available CAR‐T cell treatments 100,101 …”

Autoimmune diseases as comorbidities for liver, gallbladder, and biliary duct cancers in Sweden

“…This applies also to hepatobiliary cancers, which are increased in many patients with autoimmune diseases and specificity as to the type of autoimmune disease and cancer (e.g., HCC risk is vastly increased in patients with autoimmune hepatitis and primary biliary cirrhosis) 21,22 . Another cause of cancer in certain patients with autoimmune diseases is the immunosuppressive medication used to control the underlying disease 23,24 …”

“…21,22 Another cause of cancer in certain patients with autoimmune diseases is the immunosuppressive medication used to control the underlying disease. 23,24 We present here an updated nationwide Swedish study on hospitalized patients with autoimmune diseases (total, 929,000) and their subsequent hepatobiliary cancers (total, 18,598). Forty-three different autoimmune diseases were included and with an extended follow-up time of 8 years, the patient numbers were more than two times higher than in our previous study.…”