γδ T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival.

摘要: Merkel cell carcinomas (MCC) are immunogenic skin cancers associated with viral infection or UV-mutagenesis. To study T-cell infiltrates in MCC, we analyzed 58 MCC lesions from 39 patients using multiplex-immunohistochemistry/immunofluorescence (m-IHC/IF). CD4+ CD8+ T cells comprised the majority of infiltrating lymphocytes most tumors. However, almost half tumors harbored prominent CD4/CD8 double negative (DN) (>20% DN cells) and 12% cases, represented cells. Flow cytometric analysis single-cell suspensions fresh identified as predominantly Vδ2- γδ In context inflammation, these expressed PD1 LAG3, which is consistent a suppressed exhausted phenotype, CD103, indicates tissue-residency. Furthermore, RNA sequencing (scRNA-seq) transcriptional profile suggestive proinflammatory potential. receptor (TCR) confirmed clonal expansion Vδ1 Vδ3 clonotypes functional studies cloned TCRs demonstrated restriction for CD1c MR1 antigen-presenting molecules. Based on 13-gene cell-signature derived scRNA-seq analysis, gene-set enrichment bulk RNA-seq data showed positive correlation between scores infiltrates. An improved disease-specific survival was evident high complete responses to anti-PD1/PD-L1 treatment were observed three four cases scores. Thus, infiltration may serve prognostic biomarker should be explored therapeutic interventions.