Transplenic and transtumoral in vivo immunostimulation: effect on cellular immunity parameters

It has been shown that IL-2 and gamma-IFN own an additive immunostimulatory effect against tumors. Moreover, it has been suggested that the locoregional route of administration of immunopotentiating agents has substantial advantages compared to the systemic route. The aim of the present study was to evaluate the immune response of patients with advanced unresectable liver and pancreatic malignant disease who were submitted for transplenic and transtumoral IL-2 and gamma-IFN combination immunotherapy.

In 32 patients, the following therapeutic regimen was applied for 10 consecutive days: a) 5 days transplenic administration of 5 mg IL-2 plus 50 micrograms gamma-IFN in a Lipiodol-Urografin emulsion, and b) 5 days transtumoral administration of the same drug cocktail. In the beginning (T1) and on day 15 (T2) after treatment, the following parameters were performed: CD3+, CD4+, CD8+, IL-2r+, HLA-DR+ lymphocytes in peripheral blood spontaneously, and after 48-hour T-lymphocyte cultures in the presence of PHA.

CD3+, CD4+ and CD8+ T-lymphocytes were significantly increased in peripheral blood after treatment (p < 0.05, p < 0.05, and p < 0.003, respectively), whereas IL-2r expression and HLA-DR expression on CD4+ T-cells were not influenced significantly (p > 0.05). After PHA 48-hour T-cell cultures, T-cell subpopulations showed the following alterations: CD3+, CD4+ and CD8+ T-cells were significantly increased (p < 0.001, p < 0.006 and p < 0.01, respectively). Moreover, IL-2r expression as well as HLA-DR expression on CD4+ T-cells were also significantly increased (p < 0.001).

Locoregional treatment exerted a beneficial immunopotentiating effect on T-cell populations, IL-2r expression and HLA-DR expression. This is a promising mode of action in the management of malignant metastatic disease.