[Cancer immunotherapy: Rational and recent breakthroughs].

Area of Science:

• Oncology
• Immunology

Background:

• Cancer immunotherapy historically played a limited role, despite evidence of immune system involvement in cancer control.
• A paradigm shift now emphasizes addressing the immunosuppressive tumor microenvironment alongside immune activation.

Observation:

• Negative costimulatory molecules (e.g., CTLA-4, PD-1) on T cells within tumors can hinder anti-tumor responses.
• Blocking these molecules, such as with anti-CTLA-4 and anti-PD-1 antibodies, can restore T cell activity against tumors.

Findings:

• Anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab, pembrolizumab) antibodies are approved for metastatic melanoma.
• These immunotherapies demonstrate clinical efficacy in metastatic melanomas, lung cancers, and renal cell carcinoma.
• Early trials indicate responsiveness in other cancers, including Hodgkin's disease and head and neck cancers.

Implications:

• Cancer immunotherapies can induce autoimmune side effects due to the loss of self-tolerance.
• Optimizing combination therapies and identifying predictive biomarkers are crucial for advancing this drug class in oncology.