Malignant melanoma. Inflammatory mononuclear cell infiltrates in cerebral metastases during concurrent therapy with viral oncolysate

Abstract

Five patients with advanced malignant melanoma, treated with viral oncolysate, had solitary central nervous system metastases that were removed surgically. Histologic examination revealed striking and significant mononuclear inflammatory cell infiltrates, consisting of a mean of 60% plasma cells and a lesser proportion of lymphocytes at the edges of the lesions, within their supporting fibrovascular trabeculae, and among the tumor cells. Comparable inflammatory changes were not found in solitary metastatic malignant melanomas removed surgically from the brains of 19 patients not treated with viral oncolysate. Similarly, multiple metastatic malignant melanomas obtained postmortem from the brains of 12 patients not treated with viral oncolysate showed minimal inflammatory responses. Ultrastructural examination of material from a single treated patient revealed morphologic abnormalities of the blood-brain barrier, changes that were perhaps conducive to infiltration of the neoplasm by inflammatory cells. The authors suggest that administration of viral oncolysate enhances the inflammatory cell response to metastatic malignant melanoma in the brain.

Immunological responsiveness to interleukin-2-producing brain tumors can be restored by concurrent subcutaneous transplantation of the same tumors

“…18 -22 The CNS, however, is considered to be an immunologically privileged site where a systemic immune response fails to prevent tumor growth. [3][4][5][6][7] Sampson et al 11 reported that s.c. vaccination with irradiated, cytokine-producing tumor cells was effective for the treatment of brain tumors, but complete elimination of brain tumors was seldom achieved by this strategy. We have shown that s.c. inoculation of 9L/IL-2 cells suppressed the growth of i.c.…”

“…3,4 Impaired immunological reactions in the brain were also evidenced by other studies in experimental and clinical immunotherapies for brain tumors. [5][6][7] Recent studies, however, showed that cytokines such as interleukin-2 (IL-2), IL-4, or granulocyte-macrophage colony-stimulating factor secreted from tumor cells could suppress the growth of inoculated brain tumors, although complete elimination of the tumors was rarely observed. 8 -13 An immune response within the CNS may be different from that in other organs, but these studies indicate that the CNS is possibly subjected to cytokine-assisted immunogene therapy.…”

Regression of orthotopic brain tumors by cytokine-assisted tumor vaccines primed in the brain

“…7,11 In addition, tumors established within the CNS have failed to respond to other forms of systemic immunotherapy. [27][28][29][30] The CNS may pose a barrier to using cytokinesecreting tumor vaccine. However, according to recent evidence, the immunity elicited by the subcutaneous injection of cytokine-secreting tumor vaccines can regress tumors implanted in the brain, suggesting that the immunologically privileged CNS is not an absolute barrier to this form of active, specific immunotherapy.…”

Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.

“…The CNS, however, has been shown to be a barrier to allograft and xenograft rejection and has been considered an "immunologically privileged" site both historically (16,17) and more recently (18). Indeed, the concept that immunologic reactions against tumors within the CNS may be impaired has been supported by other studies of experimental (19) and clinical (20)(21)(22) immunotherapies where systemic responses failed to prevent tumor growth in the CNS. The CNS, then, may pose a significant barrier to the use of cytokine-assisted tumor vaccines.…”