MCSP(+) metastasis founder cells activate immunosuppression early in human melanoma metastatic colonization

To investigate the early, poorly understood events driving metastatic progression, we searched for the earliest detectable disseminated cancer cells (DCCs), also often referred to as disseminated tumor cells (DTCs), in sentinel lymph node (SLN) biopsies of 492 patients with stage I-III melanoma. Using micromanipulator-assisted isolation of rare DCCs, single-cell mRNA and DNA sequencing, codetection by indexing immunofluorescence imaging and survival analysis, we identified melanoma-associated chondroitin sulfate proteoglycan (MCSP)(+) melanoma cells as metastasis founder cells (MFCs). We found that DCCs entering SLNs predominantly exhibited a transitory phenotype that, upon interferon-

• Guetter, S.
• König, C.
• Koerkel-Qu, H.
• Markiewicz, A.
• Scheitler, S.
• Katzer, M.
• Berneburg, M.
• Renner, P.
• Cucuruz, B.
• Guttenberger, L.
• Naimer, V.
• Weidele, K.
• Treitschke, S.
• Werno, C.
• Jaser, H.
• Bargmann, T.
• Braun, A.
• Weber, F.
• Evert, K.
• Rochwarger, A.
• Schürch, C. M.
• Limm, K.
• Oefner, P. J.
• Rachel, R.
• Baumann, F.
• Warfsmann, J.
• Schmidleithner, L.
• Guetter, K.
• Mohammadi, P.
• Ulmer, A.
• Haferkamp, S.
• Klein, C. A.
• Werner-Klein, M.