Personalized therapy for metastatic melanoma: could timing be everything?

Abstract

There is ample evidence that immune-related processes in humans are under temporal regulation. The circadian variation of humoral and cellular immunity is well documented and appears to be hormonally modulated via the hypothalamic–pituitary–adrenal axis. In advanced melanoma, it has recently been demonstrated that systemic immunity is repolarized toward a global state of chronic inflammation (Th2 dominance) and appears to be governed by infradian biorhythms of cytokines and immune cell subsets, which extend beyond the 24-h circadian variability reported in healthy volunteers. It is suggested that synchronizing administration of lymphodepleting chemotherapy (temozolomide) with these endogenous (individualized) immune dynamics (biorhythms) in patients with advanced/metastatic melanoma improves clinical outcomes compared with temozolomide used in a conventional ‘random delivery’ fashion.