Transcript Tumor Immunology

Cytokines Play an Essential Role in
Intercellular Communication
Cytokine
Produced by
Function
Interferon-
Leukocytes
Increases MHC I expression
Interferon-g
T cells, NK cells
Activates macrophages;
increases MHC expression;
suppresses TH1 responses
Interleukin-2 (IL-2) T cells
Induces T-cell proliferation
and differentiation
Interleukin-10
T cells, macrophages
Suppresses immune function
Transforming
growth factor
(TGF-b)
T cells, monocytes
Inhibits cell growth
Tumor necrosis
factor (TNF)
T cells, NK cells
Induces inflammatory
response
Asadullah K, et al. Clin Exp Dermatol. 2002;27:578-584.
Tumor Necrosis Factor
• 1890s: William Coley
Coley’s Toxin: Bacterial preparation of Streptococcus pyogenes
- First published cancer immunotherapy paper
Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas:
with a report of ten original cases. Am. J. Med Sci. 1893; 105: 487-511.
- Treated ~ 900 patients presenting with inoperable cancers.
- 10% cure rate
Interleukin-2
• T cell growth factor
• Induces the activation and proliferation of
cytotoxic T-lymphocytes
• Enhances the cytolytic ability of NK cells
• Mediates antitumor activity in vivo
December, 1985
Interleukin-2 Toxicity
• Commonly: Fever, chills, lethargy, diarrhea,
nausea, anemia, confusion.
• Induces a capillary leak syndrome with major
fluid shifts.
– Hypotension, Azotemia
– ICU monitoring, vasopressors
• Neutrophil chemotactic defect predisposing
patients to gram positive bacteria.
• Mortality of 1% (down from 5%).
Interleukin-2 and Melanoma
Renal Cell Carcinoma
• High Dose IL-2
– 600,000 to 720,000 IU/kg IV q8o on days 1-5 and 15 -19.
– Repeat at 8 to 12 week intervals in responding patients
• Tumor Response: 15-20%
• Complete Response: 4-6% and durable.
IL-2 approved for metastatic melanoma in 1993 and for
RCC later.