Abstract:

Interferon-alpha (IFN-alpha) has been found to exert multiple enhancing effects in the immune response in vitro, IFN-alpha has been also used in clinical trials with variable response rates. The aim of the present study was to assess the effectiveness of IFN-alpha in the treatment of 25 patients with malignant pleural or peritoneal effusions caused by lung, and metastatic breast and ovarian cancer. Clinical responses were correlated with a) the ratio of malignant effusion (ME)-associated tumor cells to ME-associated mononuclear cells (MEMNC), b) MEMNC-derived cytotoxic responses against autologous or allogeneic tumor targets, and c) major histocompatibility complex (MHC) antigen expression on tumor cells. After partial drainage of pleural or peritoneal fluid, the patients were allocated to receive 10 million units of IFN-alpha by intrapleural or intraperitoneal injection at weekly intervals. The treatment was terminated if the malignant effusion disappeared or the patients had received four to six consecutive procedures. None of the patients received concomitant systemic chemotherapy or radiation therapy. MEMNC and tumor cells were isolated by centrifugation on discontinous percoll density gradients. Cytotoxic and phenotypic profiles of MEMNG were analyzed before and after treatment with IFN-alpha. An improvement was observed in patients with increased ratios of tumor cells to malignant effusion-associated mononuclear cells (MEMNC) in the effusions. In the same patients MEMNC were overpopulated by CD8+ T lymphocytes. In this group of patients the administration of IFN-alpha was associated with 25% complete response and 75% partial response rates. In contrast only 17% partial responses were achieved in patients whose effusions had decreased tumor cell to MEMNC ratios. The immunomodulation induced by IFN-alpha in vivo was also tested. Thus in a group of 6 patients, treatment with IFN-alpha resulted in the induction of CD8+ cell-mediated lysis against autologous tumor cells which was associated with PR (two patients). Natural killer (NK)-cell activity, and MHC class I antigen expression on effusion-associated tumor cells were also enhanced during treatment, but were not correlated with the outcome of the therapy since similar findings were also observed in the 4 non-responders. Local infusions of IFN-alpha provide an effective alternative treatment for malignant effusion in patients with lung, breast, and ovarian cancer. Increased ratios of tumor cells to MEMNC and the presence of CD8+ T lymphocytes within the malignant effusions may play an important role in the outcome of such a treatment with IFN-alpha but more patients need to be studied for definite conclusions.

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