Immune Parameters in The Prognosis and Therapy Monitoring of Cutaneous Melanoma Patients: Experience, Role, and Limitations

Abstract

Cutaneous melanoma is an immune-dependent aggressive tumour. Up to our knowledge, there are no reports regarding immune parameters monitoring in longitudinal followup of melanoma patients. We report a followup for 36 months of the immune parameters of patients diagnosed in stages I–IV. The circulatory immune parameters comprised presurgery and postsurgery immune circulating peripheral cells and circulating intercommunicating cytokines. Based on our analysis, the prototype of the intratumor inflammatory infiltrate in a melanoma with good prognosis is composed of numerous T cells CD3+, few or even absent B cells CD20+, few or absent plasma cells CD138+, and present Langerhans cells CD1a+ or langerin+. Regarding circulatory immune cells, a marker that correlates with stage is CD4+/CD8+ ratio, and its decrease clearly indicates a worse prognosis of the disease. Moreover, even in advanced stages, patients that have an increased overall survival rate prove the increase of this ratio. The decrease in the circulating B lymphocytes with stage is balanced by an increase in circulating NK cells, a phenomenon observed in stage III. Out of all the tested cytokines in the followup, IL-6 level correlated with the patient's survival, while in our study, IL-8, IL-10, and IL-12 did not correlate statistically in a significant way with overall survival, or relapse-free survival.

Inflammation markers in cutaneous melanoma - edgy biomarkers for prognosis

“…The authors highlight a very interesting immune mechanism in which LCs in melanoma patients migrate from the skin to SLNs having an immature phenotype, this phenotype induces a tolerogenic milieu for melanoma associated antigens 48 . When we have studied our group of patients, we have scarcely found LC within tumor mass, and, when present, LCs were negatively correlated with Breslow index (higher the pT level, more probable absence of LC), but not with ulceration 31 . However, when correlating LC and pT level separately in ulcerated and non-ulcerated tumors, we have identified their presence in thinner tumors.…”

“…Our data indicate the presence of abundant TILs within thick ulcerated tumors (unfavorable prognosis). In our opinion, more likely this infiltration represents a normal enhancement of the inflammatory infiltrate within an ulcerated tumor as a physiologic reaction to ulceration 31 . The activation degree of T lymphocytes CD4(+) was investigated evaluating membrane CD134 expression (OX40), this molecule being a member of the TNFR-superfamily expressed on activated T cells.…”

“…In the cases we have published, presence of more numerous B cells in ulcerated tumors may be secondary to ulceration (as part of subsequent inflammatory reaction) and therefore should not be regarded as indicator of bad prognosis. Plasmocytes CD138(+) were present in almost all areas of regression and, when present, they were frequent, irrespective of regression type or ulceration 31 . A subset of B-lymphocytes (B-1) was reported as having in vivo pro-metastatic effects on melanoma cells through a direct cell-cell interaction.…”

“…When analyzing mature T cells CD7(+) we have seen an overall tendency of losing CD7(+) expression in inflammatory infiltrate both intratumor and in regression areas. At tumor site there is a slight predominance of CD4(+) cells uncorrelated with pT level, ulceration or regression 31 . B lymphocytes CD20(+) are increased in pT4 tumors and prevail in ulcerated tumors.…”

“…This phenomenon was shown to be a consequence of defective MDSC function and reliant upon activation of CD8(+) T cells 30 . Analyzing over 100 melanoma patients, we have shown that the inflammatory infiltrate in regressed and non-regressed tumor components, have different distribution of inflammatory cells 31 . Inflammatory infiltrate consists mainly of T lymphocytes CD3(+) as previously reported 32,33 .…”