Skip to Content
MilliporeSigma
  • Immune-escape markers in relation to clinical outcome of advanced melanoma patients following immunotherapy.

Immune-escape markers in relation to clinical outcome of advanced melanoma patients following immunotherapy.

Cancer immunology research (2014-06-05)
Esther P M Tjin, Gabrielle Krebbers, Kimberley J Meijlink, Willeke van de Kasteele, Efraim H Rosenberg, Joyce Sanders, Petra M Nederlof, Bart A van de Wiel, John B A G Haanen, Cornelis J M Melief, Florry A Vyth-Dreese, Rosalie M Luiten
ABSTRACT

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 before autologous tumor cell vaccination, and 16 patients who were intended to treat but were not vaccinated because of 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/PD-L1, IDO, and galectins), cytotoxic molecules (granzyme-B), melanocyte differentiation antigens, HLA class-I and tolerogenic cytokines [interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-β] 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 nonprogressors to vaccination (n = 9; median OS, 56 months), compared with progressors (n = 18; median OS, 9.5 months). Moreover, granzyme-B expression was elevated in the tumors of nonprogressors, suggesting activated cytotoxic T cells 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 with those from patients with rapid progression (not vaccinated; n = 16; median OS, 3 months). Our study shows that high numbers of intratumoral activated CD4(+) or CD8(+) T cells, before autologous tumor cell vaccination, are associated with favorable clinical outcome. Analyses of these markers in the patients' tumor tissues before immunotherapy may therefore be a valuable tool to select patients for whom the treatment may result in potential clinical benefit.

MATERIALS
Product Number
Brand
Product Description

Supelco
Hydrogen peroxide solution, ≥30%, for trace analysis
Sigma-Aldrich
Hydrogen peroxide solution, 34.5-36.5%
Sigma-Aldrich
Hydrogen peroxide solution, tested according to Ph. Eur.
Sigma-Aldrich
Hydrogen peroxide solution, contains potassium stannate as inhibitor, 30-32 wt. % in water, semiconductor grade, 99.999% trace metals basis
Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
Hydrogen peroxide solution, SAJ first grade, ≥30.0%
Millipore
Hydrogen peroxide solution, 3%, suitable for microbiology
Sigma-Aldrich
Hydrogen peroxide solution, contains ~200 ppm acetanilide as stabilizer, 3 wt. % in H2O
Sigma-Aldrich
Hydrogen peroxide solution, purum p.a., ≥35% (RT)
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, meets USP testing specifications
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 30 wt. % in H2O, ACS reagent
Sigma-Aldrich
Hydrogen peroxide solution, contains inhibitor, 35 wt. % in H2O
Sigma-Aldrich
Hydrogen Peroxide Solution, 30% (w/w), puriss. p.a., reag. ISO, reag. Ph. Eur.
Sigma-Aldrich
Hydrogen peroxide solution, 50 wt. % in H2O, stabilized
Supelco
Hydrogen peroxide solution, 30 % (w/w), for ultratrace analysis
Sigma-Aldrich
TNF-α human, Animal-component free, recombinant, expressed in E. coli, suitable for cell culture
Sigma-Aldrich
Tumor Necrosis Factor-α human, TNF-α, recombinant, expressed in E. coli, powder, suitable for cell culture
Sigma-Aldrich
Tumor Necrosis Factor-α human, Xeno-free, recombinant, expressed in HEK 293 cells, suitable for cell culture
Sigma-Aldrich
Anti-Indoleamine 2,3-dioxygenase Antibody, clone 10.1, clone 10.1, Chemicon®, from mouse