Adjuvant cytokine treatment of minimal residual disease after surgical therapy in mice carrying HPV16-associated tumours: cytolytic activity of spleen cells from tumour regressors.

It has been found previously that IL-2, IFNγ and GM-CSF were capable of reducing the recurrence rate of HPV 16-associated tumours in mice with SMRTD. We were interested whether the therapeutic effect of the surgery and adjuvant cytokine treatment was accompanied by cytolytic activity of spleen cells and whether the activity of the spleen cells was different in mice that had rejected tumour residua after surgery and adjuvant therapy with cytokines (tumour regressors) as compared to those that had not rejected the tumour residua (tumour progressors). We have examined the cytolytic activity of spleen cells from MHC class I + TC-1 tumour regressors and progressors after treatment of TC-1 SMRTD with GM-CSF, and the activity of spleen cells from MHC class I - MK16 tumour regressors and progressors after treatment of MK16 SMRTD with IL-2 and IFNy. It has been found that irrespective of the tumour type and adjuvant treatment, the spleen cells from tumour regressors after surgery were regularly more cytolytic when allowed to react with target cells from HPV 16-associated tumours than the spleen cells from tumour progressors. No substantial differences between the cytolytic activity of spleen cells from the operated-only and operated plus cytokine (GM-CSF, IL-2, IFNγ) adjuvant treated groups were observed. The cytolytic activity of spleen cells from mice with SMRTD allowed to react with MHC class I + , MHC class I - , NK-sensitive and NK-resistant targets is compatible with the interpretation that in the mice with MHC class I + TC-1 tumours, primarily cytotoxic T lymphocytes (CTL) were efficient, whereas in the mice with MHC class I - MK16 tumours, both NK and non-lymphocytic effector cells were involved.