Based on evidence of significant expansion and differentiation of the humoral response in the TME, we investigated the expression of AICDA (AID, encoding the enzyme activation-induced cytidine deaminase, crucial for SHM and CSR), and of recombination-activating genes RAG1 and RAG2 (involved in V(D)J recombination) in normal skin (n = 555) and cutaneous melanoma skin metastases (n = 116) (TCGA TARGET GTEx (UCSC Xena)) (Fig. 5f–h). Here, RAG2 is linked to cutaneous melanoma.