DOCK2 modulates immune checkpoint inhibitor responsiveness and prognosis in cutaneous melanoma through multi-omics and single-cell T cell dynamics profiling.

[BACKGROUND] Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy that arises from melanocytes and has been associated with a notable increase in incidence and mortality rates across the globe. The current treatment modalities for SKCM, which encompass surgical interventions, radiotherapy, chemotherapy, and immunotherapy, have notably enhanced survival outcomes for certain patient subsets. Nonetheless, these approaches are frequently limited by factors such as variable efficacy, adverse side effects, and the emergence of resistance mechanisms. In this context, there is a pressing need to explore novel therapeutic targets that may enhance treatment effectiveness.

[METHODS] This study examines the Dedicator of cytokinesis 2 (DOCK2) gene, which has been implicated in immune regulation, yet its functional roles within oncogenesis, particularly in melanoma, remain inadequately characterized. We employed an integrated bioinformatics approach utilizing clinical datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression project (GTEx), and the Human Protein Atlas (HPA) to evaluate DOCK2 expression across various malignancies and to assess its prognostic significance in SKCM.

[RESULTS] Our analyses revealed that DOCK2 expression is differentially modulated across several cancer types and serves as a favorable prognostic marker specifically in SKCM. Notably, elevated DOCK2 levels were significantly correlated with improved therapeutic responses to immune checkpoint inhibitors (ICIs), suggesting that DOCK2 may play a pivotal role in modulating the tumor immune microenvironment. Furthermore, functional enrichment analyses indicated that DOCK2-associated genes are critically involved in vital immune pathways, encompassing leukocyte-mediated immunity and immune receptor activity. Increased expression of DOCK2 was also associated with heightened T cell infiltration in SKCM tumor tissues.

[CONCLUSIONS] Collectively, these findings highlight the promising prognostic and therapeutic implications of DOCK2 in melanoma, emphasizing its potential as a biomarker for assessing immunotherapy efficacy. Our research advocates for further investigation into DOCK2 as a viable target for precision immunotherapy, which could ultimately lead to improved treatment strategies for patients battling SKCM.