Toxicities of Immunotherapy for the Practitioner

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Cancer immunotherapies encompass diverse treatments like cytokine therapy, vaccines, cell therapy, and checkpoint inhibitors.
• These treatments, while effective, can lead to significant toxicities.
• A common mechanism underlying these toxicities is immune-related adverse events (irAEs).

Purpose of the Study:

• To review the spectrum of toxicities associated with various cancer immunotherapies.
• To elucidate the shared mechanism of T-cell-mediated adverse events across different immunotherapy types.
• To highlight the importance of recognizing and managing these irAEs for oncology practitioners.

Main Methods:

• Literature review of existing studies on cancer immunotherapy toxicities.
• Analysis of the immunological mechanisms driving irAEs.
• Categorization of toxicities based on immunotherapy type (cytokines, vaccines, cell therapy, checkpoint inhibitors).

Main Results:

• Immunotherapy toxicities are diverse, ranging from capillary leakage to autoimmunity and organ damage.
• A unifying mechanism is the hyperactivated T-cell response directed against normal tissues.
• Both CD4 T-helper and CD8 cytotoxic T cells play roles in irAEs, leading to cytokine release or tissue infiltration.
• Specific therapies activate T cells differently, influencing the pattern of organ damage.

Conclusions:

• Cancer immunotherapies share a common T-cell-mediated mechanism for their toxicities.
• Understanding the specific T-cell responses and resulting irAEs is vital for effective patient management.
• Oncology practitioners must be familiar with the evolving landscape of immunotherapy-induced adverse events.