In this study, we investigated a large series of immune (escape) markers, relevant to T-cell function, as potential biomarkers for clinical outcome following immunotherapy. We retrospectively studied the expression of immune (escape) markers in metastatic melanoma tissues of 27 patients prior to autologous tumor-cell-vaccination and 16 patients who were intended to treat but after all not vaccinated due to rapid disease progression. Immunohistochemical data of infiltrating (suppressive) cells, such as T-cells, regulatory T-cells, myeloid-derived-suppressor cells and mast cells, or the expression of T-cell inhibitory factors (PD-1/PDL-1, IDO, galectins), cytotoxic molecules (granzyme-B), melanocyte-differentiation-antigens, HLA class-I and tolerogenic cytokines (IL-1, IL-6, IL-10, TNFα, TGFβ) were correlated statistically to clinical outcome and overall survival (OS). Significantly more tumor-infiltrating CD4+ and CD8+ T-cells (both P<0.05) were found in non-progressors to vaccination (n=9;median OS=56 months), compared to progressors (n=18;median OS=9.5 months). Moreover, granzyme-B expression was elevated in the tumor of non-progressors, suggesting activated cytotoxic T or natural killer cells. T-cell infiltration and granzyme-B expression significantly correlated with overall OS. T-cell inhibitory factors and suppressive cells did not correlate with OS, suggesting minor influence of these immune escape markers on clinical outcome. The data of progressors were comparable to patients with rapid progression (not vaccinated)(n=16;median OS=3 months). Our study shows that high numbers of intra-tumoral activated CD4+ or CD8+ T-cells, prior to autologous tumor cell vaccination, are associated with favorable clinical outcome. Analyses of these markers in patients' tumor tissues prior to immunotherapy may therefore be a valuable tool to select patients with potential clinical benefit.
- Received July 16, 2013.
- Revision received January 24, 2014.
- Accepted February 28, 2014.
- Copyright © 2014, American Association for Cancer Research.