Most vaccination studies of
cancer patients find no clear association between clinical and immunological responses to the
vaccine. We discuss the possible kinetics of the T cell response in
melanoma patients against unique or shared
tumor antigens. We hypothesize that a response against unique
antigens prevails during primary
melanoma growth, causing the selection of
tumor cells lacking most of these
antigens unless these are necessary to maintain the neoplastic state. After a subset of
tumor cells metastasize to the lymph nodes, T cells are activated against previously ignored shared, differentiation-like
antigens, owing to a new environment where pro-inflammatory
cytokines can be present. The development of a T cell response to such normal
epitopes then associates with
tumor growth, but remains clinically inefficient. We predict that two immunologically different subsets of
melanoma patients may exist, one that mounted an early immune response against
melanoma antigens and one that did not. A paradox may emerge when vaccination is attempted in these two groups of subjects, with the second group being more prone to develop an effective immune response if the
vaccine is potent enough to activate naive T cells, while the first has probably already eliminated most of the
tumor antigens potentially recognizable by the host T cells owing to the previous selection made by the immune response developed early during
tumor growth. Thus, it is likely that the subgroup of metastatic patients with a high frequency of anti-
melanoma memory T cells may not show a clinical response to vaccination.