Lecture on Immunology and Cancer Treatment

Continuous Glucose Chemotherapy

• Introduction to Continuous Glucose Chemotherapy:

  • The therapy has been implemented in children with limited options for treatment.

  • Example: Six children treated; three became long-term survivors.

• Case Study:

  • Focus on a child with a tumor located in the spine.

  • Received metronomic chemotherapy for 4-5 years.

  • The tumor was controlled, demonstrating no growth over time.

• Broader Research:

  • Studies indicate success in similar pediatric cases, especially in areas lacking treatment options.

Immune System Functionality

• Overview of the Immune System:

  • The immune system detects and kills foreign cells, including cancer.

  • Types of Cells:

  • Cytotoxic T Cells: Attack foreign structures if activated.

  • Natural Killer Cells: Attack without prior activation if foreign content is present.

• Mechanisms of Tumor Evasion:

  • Tumor cells can lose MHC class I molecules, preventing the immune system from recognizing them as dangerous.

  • Selective pressures in tumors lead to gene silencing of MHC class I to avoid detection.

• Implications of T Cell Memory:

  • Once the immune system recognizes a specific tumor type, it retains memory—leading to long-term protection from that specific cancer even after years.

Cell Death Processes: Apoptosis vs. Necrosis

• Apoptosis (Programmed Cell Death):

  • Is a clean process where cells undergo self-destruction neatly without triggering inflammation.

  • The immune system does not learn from cells that die this way since the debris is not left for antigen presentation.

• Necrosis:

  • Occurs due to external damage, leading to inflammation.

  • It plays a role in stimulating the immune response as the contents of dying cells spill out, potentially allowing for antigen presentation.

Cancer Treatments and Risks

• Organ Transplantation Risks:

  • Immunosuppression increases the risk of developing certain cancers, indicating the importance of an active immune system for cancer surveillance.

  • Donor-recipient matching is crucial to minimize rejection and improper immune responses.

• Tumor Infiltrating Lymphocytes (TILs):

  • High levels of TILs in tumor samples often correlate with better patient prognosis.

  • Lack of lymphocyte presence generally indicates poorer outcomes.

Factors Contributing to Childhood Cancers

• Burkitt's Lymphoma in Sub-Saharan Africa:

  • Accounts for up to 50% of childhood cancers, particularly in ages 4 to 7.

  • Treatment success rates show 85-90% for children through intense chemotherapy, lesser in adults (60-70%).

• Rapid Tumor Growth:

  • Burkitt's lymphoma can double in size within 24-48 hours, making rapid treatment essential.

New Cancer Immunotherapy Approaches

• CTLA-4 and Immune Modulation:

  • CTLA-4 acts as a brake on T cells; targeting this pathway can enhance anti-tumor immunity.

  • Designing antibody therapies against CTLA-4 shows promise in significantly increasing overall survival rates in cancer treatments.

• Case Example of Treatment Efficacy:

  • Clinical trial results from 2010 show remarkable median survival improvements and long-term survival rates for patients receiving novel CTLA-4-targeted immunotherapy.

Patient Testimonials and Outcomes

• Personal Stories of Treatment Success:

  • Sharon Belvo's experience highlights the effectiveness of CTLA-4 therapy: her tumors diminished in size following the treatment after failing previous chemotherapy and radiation.

  • The variability in individual responses to immunotherapy and the potential for autoimmune effects are discussed, emphasizing the importance of immune system balance in cancer treatment.