Lecture Notes: Immune System and Immunotherapy in Cancer Treatment

The Immune System

• Function: Defends the body against foreign invaders such as viruses, bacteria, and cancer cells.
• Key Cells:
  • T-cells: Release toxins to destroy invaders.
  • B-cells: Produce antibodies to neutralize invaders.

Mechanism of Action

• Cell Surveillance: T-cells scan cell surfaces for abnormal peptides presented by MHC or HLA molecules using T-cell receptors (TCR).
• Action Upon Detection: If foreign peptides are detected, T-cells activate and release cytokines to destroy the invader.

Cancer and the Immune System

• Cancer Recognition: T-cells can recognize cancer cells as foreign due to mutated proteins presented as peptides.
• Immune System Failures: Despite recognition, immune responses might be weak or cancer cells might evade detection.
• Tumor Defense Mechanisms:
  • Expression of inhibitory checkpoints (e.g., PD-1, CTLA-4) that weaken T-cells.
  • Secretion of factors that suppress T-cell activity and transform them into T-regulatory cells.

Immunotherapy

• Significance: Considered a groundbreaking advancement in medicine to treat cancer.

Types of Immunotherapy

1. Enhancing the Immune System

   • Vaccines: Develop cancer vaccines using neoantigens to train T-cells.
   • Adoptive T-cell Transfer: T-cells extracted, modified, and reinfused into patients.
   • Cytokines: Use stimulating proteins (e.g., IL-2, IL-7) to boost T-cell multiplication.
   • Agonist Antibodies: Enhance T-cell strength with antibodies like anti-Ox40.

2. Inhibiting Tumor Defense

   • Antibodies: Neutralize inhibitory factors (e.g., anti-IL-10, anti-TGF-beta).
   • Checkpoint Inhibitors: Drugs target checkpoints like PD-1 and CTLA-4.
   • Clinical Trials: Combination therapy with CTLA-4 and PD-1 antibodies improves survival in advanced melanoma.

Side Effects and Monitoring

• Common Side Effects: Diarrhea, endocrine disruptions, thyroid dysfunction, diabetes.
• Management: Side effects are treatable if identified early; monitoring is crucial.

Future of Immunotherapy

• Goals:
  • Develop a robust immune army to attack cancer.
  • Break cancer defenses to enhance patient outcomes.
• Strategies: Combining different immunotherapy approaches to improve results.