Immunological factors influencing clinical outcome in lung cancer XXXX after telomerase peptide vaccination.

@entity1 @entity137 @entity5750 @entity9536 @entity1149 @entity2902 @entity3646 @entity688 @entity1116
UNASSIGNED: We have previously reported two trials in @entity1149 ( @entity1149 ) evaluating vaccine therapy with the telomerase peptide GV1001. The studies demonstrated considerable differences in survival among immune responders, highlighting that an immune response is not necessarily beneficial. In the present study, we conducted long-term clinical follow-up and investigated immunological factors hypothesized to influence clinical efficacy. Peripheral blood mononuclear cells from 33 @entity1149 trial @entity1 and 15 healthy donors were analyzed by flow cytometry for T regulatory cells (Tregs, CD4(+) @entity2902 (+)CD127(low/-)FOXP3(+)) and two types of myeloid-derived suppressor cells (MDSCs, HLA-DR (low) @entity5750 (+) or Lin (-/lo) HLA-DR (-) @entity1116 (+) @entity9536 (+)). T cell cultures were analyzed for 17 cytokines. The results demonstrated that immune responders had increased overall survival (OS, p  <  0.001) and progression-free survival (p  =  0.003), compared to subjects without immunological response. The mean OS advantage was 54 versus 13  months. Six @entity1 were still alive at the last clinical update, all belonging to the immune responders. No serious @entity137 had developed (maximum observation 13  years). Most @entity1 developed a polyfunctional cytokine profile, with high IFNy/ @entity3646 and IFNy/ @entity688 ratios. Low Treg levels were associated with improved OS (p  =  0.037) and a favorable cytokine profile, including higher IFNy/ @entity688 ratios. High @entity1116 (+) MDSC levels were associated with poorer immune response rate (p  =  0.005). The levels of @entity5750 (+) MDSC were significantly higher in @entity1 than in healthy controls (p  =  0.012). We conclude that a randomized GV1001 trial in @entity1149 is warranted. The findings suggest that Tregs and MDSCs are associated with a tolerogenic cytokine milieu and impaired clinical efficacy of vaccine responses.
