MECHANISTIC CLASSIFICATION OF IMMUNE CHECKPOINT INHIBITOR TOXICITY AS A POINTER TO MINIMAL TREATMENT STRATEGIES TO FURTHER IMPROVE SURVIVAL
- Dennis McGonagle, United Kingdom
Abstract
Background and Aims
Improved anti-tumour responses under immune checkpoint inhibition (ICI) are associated with concomitant autoimmune disease development termed immune-related adverse events (irAEs), of which approximately 5% are rheumatic in nature. We have reviewed the literature to assess whether immunosuppression therapy of irAEs may negatively affect the patient's outcome.
Methods
Review of the literature
Results
Oncologists and other specialists vigorously treat irAEs in spite of the generally accepted beneficial effect of irAEs on tumour survival. Herein, we highlight mechanistic insights on how tumour responses and certain types of autoimmunity appear to be inextricably linked around CD8+ T-cell mediated responses and those strategies that interfere with such shared immunopathogenesis could impact survival. We discuss the possible circumstances in which intensive immunosuppressive therapy for irAEs that occur with ICIs might blunt anti-tumour immunity. We also discuss potential therapeutic strategies for emergent ICI related autoimmunity and propose some treatment considerations and research questions to minimize the impact of overzealous immunosuppression strategies on tumour responses. Thus, refraining from using powerful therapeutic armamentarium to treat irAEs, especially when these are not considered as life-threating might improve the prognosis of ICI therapy.
Conclusions
Permitting the controlled “fire burning” of an activated immune response to ultimately stall cancer progression and further improve long-term survival is a strategy, which merits consideration. Adopting the view that survival is better in cases with irAEs who receive corticosteroids compared to subjects who do not develop irAEs is potentially ignoring the further improved survival attainable by letting the immune fire continues to burn.