Tumor infiltrating lymphocytes derived from metastatic melanoma during intralesional immunostimulatory therapy exhibit a phenotype reflecting tumor progression (P2193)

Abstract

Abstract Intralesional immunostimulatory therapy is a rational approach for in transit metastatic melanoma, as lesions are accessible and provide a source of matched tumor antigen to facilitate local and systemic immune responses. Moreover, the lesions are accessible for evaluation of the local immune response at the site of disease. To examine the immunological status at the site of disease during the course of intralesional therapy, T cells were extracted from lesions, cultured to preserve their in vivo phenotype, and expanded for functional analysis. T cells isolated from the skin lesions two weeks after initiation of intralesional therapy produced elevated Th1 cytokines relative to pre-therapy lesions. In contrast, T cells isolated at nine weeks produced decreased Th1 cytokines, but elevated Th2 cytokines, soluble IL-2Ra and IL-6, mediators associated with tumor progression. Expression of skin homing receptor cutaneous lymphocyte antigen (CLA) on lesion derived T cells correlated with Th1 cytokine production. Strikingly, lesion-derived Th1 cytokines and CLA expression were inversely correlated with tumor size during the course of therapy, whereas the phenotype of T cells derived from the blood did not change dramatically over the course of the therapy. Our studies indicate that T cells isolated from the site of disease in melanoma provide insight into the clinical state of the patient and suggest that they are critical regulators in the progression of tumor in malignant melanoma.