Figure 5. Levels of CD4⁺CCR10⁺ TEMs and CCR10⁺CLA⁺ T cells modulated by distant metastases dictate MMel prognosis.

(A) CCR10 expression on CD4⁺ TEMs is depicted for HVs and patients presenting with only cutaneous/LN (Cut + LN) metastases, additional lung (Lung) involvement, disseminated disease (Multi), and distant metastases plus lung involvement (Multi + lung) at the time of inclusion in 1 of the 3 protocols described in the Methods. (B) Match-paired comparisons of CCR10 expression (performed by flow cytometry) in all CD4⁺ T cell subsets from blood and tumors at the time of surgery in the prospective cohort of 20 patients with MMel. (C) CD4⁺CCR10⁺ T cell cytokine profile. Flow cytometry–guided sorting based on CCR10 expression in blood CD4⁺ T cells in 1 representative patient (out of 2 yielding similar results) to analyze cytokine release after a 40-hour CD3/CD28 bead–driven stimulation. (D) Kaplan-Meier survival curves of 57 patients with MMel according to the median of their proportions of circulating CD4⁺CCR10⁺ TEMs (of note, identical results with TCMs are not shown). (E and F) Same as as in B and C, showing the subset of double-positive CCR10⁺CLA⁺CD4⁺ T cells. (G) Same as in D, analyzing OS as a function of CCR10/CLA CD4⁺ T cell subsets. Each point represents 1 patient specimen, and the total number is indicated for all subpopulations studied. Statistical analyses were performed by beta regression (A), linear mixed-effects (B and E), and Cox regression (D and G) modeling. Raw P values are indicated.