Humoral and cellular immune responses in stage III-IV melanoma patients: Implications for immunotherapy

Abstract Introduction: To assess humoral and cytotoxic T lymphocyte responsiveness in melanoma patients undergoing immunotherapy trials. Methods: 24 stage III (n = 5) and stage IV (n = 19) melanoma patients underwent immunization with a recombinant vaccinia virus encoding 3 tumor associated epitopes (TAA: gp100280-288, Mart-127-35, tyrosinase1-9) and CD80/CD86 costimulatory molecules (rVV). Immunization occured i.d. in a first trial (17 patients) and intranodally in a second, ongoing trial (7 patients). Frequencies of CTL precursor (CTLp) specific for TAA or influenza matrix (IM) control epitope were quantified. Humoral response against rVV was measured by ELISA. Results: Depending on specific responses to immunization patients were ranked as good responders (responsive to 3 or 2 epitopes) or poor responders (unresponsive or responsive to 1 epitope). All stage III patients showed CTL responses against all 3 epitopes. In contrast (p rVV specific humoral response was increased (OD > 50% of pre-treatment) in all stage III patients, but only in 6/13 stage IV patients (p Conclusions: Immunocompromission in stage IV melanoma patients might hamper the induction of tumor specific CTL responses. Conversely, induction of rVV specific humoral responses doesn't prevent the generation of CTL specific for TAA. These data suggest that stage III patients and immunocompetent stage IV patients are more likely to respond to immunotherapy.