Abstract
We have reported that patients with metastatic melanoma treated with an autologous, dinitrophenol-modified vaccine develop inflammatory responses at tumor sites. Histologically, these inflamed lesions are characterized by T cell infiltration, which is sometimes associated with tumor cell destruction. We tested biopsy specimens of eight subcutaneous metastases that had developed inflammation following vaccine treatment for expression of mRNA for interferon γ(IFNγ), interleukin-4 (IL-4), tumor necrosis factor α (TNFα), and IL-10. Post-vaccine, inflamed biopsies contained mRNA for IFNγ (5/8), IL-4 (4/8) or both (3/8), and for TNFα (4/7). In contrast, IFNγ mRNA was detected in only 1/17 and TNFα mRNA in 2/16 control specimens (pre-treatment lymph node metastases or non-inflamed subcutaneous metastases). mRNA for IL-10, a cytokine with anti-inflammatory properties, was detected in 24/25 melanoma metastases and was independent of lymphoid content; in situ the reverse transcriptase/polymerase chain reaction confirmed that melanoma cells were the major source. These findings may provide a new parameter by which to measure the effects of cancer immunotherapy.
Key words: Cytokine mRNA, DNP-vaccine, Metastatic melanoma, IFNγ, IL-4, IL-10, TNFα
Footnotes
This work was supported by USPHS grants CA55322 and CA39248 and by a grant from the Nat Pincus Trust
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