Skewed Differentiation of Circulating Vγ9Vδ2 T Lymphocytes in Melanoma and Impact on Clinical Outcome

ObjectiveThe aim of this study was to evaluate over time circulating γδ T lymphocytes in melanomapatients in terms of frequency, effector functions, and relationship with clinical stage andevolution, by comparing preoperative values to those obtained at a mean follow-up of 36months or in the event of recurrence or disease progression, and to those of healthy controls.Also, we correlated the presence of tumor-infiltrating γδ T lymphocytes with clinicalevolution of melanoma.ResultsMean frequencies of circulating γδ T cells before and after melanoma removal were verysimilar and comparable to healthy subjects, but patients who progressed to stage III or IVshowed a significantly decreased frequency of circulating Vγ9Vδ2 T cells. The distributionof Vγ9Vδ2 memory and effector subsets was similar in healthy subjects and melanomapatients at diagnosis, but circulating γδ T cells of patients after melanoma removal had askewed terminally-differentiated effector memory phenotype. Highly suggestive of progressivedifferentiation toward a cytotoxic phenotype, Vγ9Vδ2T cells from patients at follow uphad increased cytotoxic potential and limited cytokine production capability, while the oppositepattern was detected in Vγ9Vδ2T cells from patients before melanoma removal.ConclusionsFollow-up data also showed that tumor infiltrating γδ T cells were significantly associatedwith lower mortality and relapse rates, suggesting that they may serve as a prognostic biomarker,for human melanoma