Research ArticleCutaneous T Cell Lymphoma

Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients

Science Translational Medicine  18 Jan 2012:
Vol. 4, Issue 117, pp. 117ra7
DOI: 10.1126/scitranslmed.3003008

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Resolving Cutaneous T Cell Lymphoma

Becoming more active figures prominently in many New Year’s resolutions. We vow to get off the couch, or up from the lab bench, and get in shape. Yet, after a 2- to 3-week frenzy, spaces appear in gym parking lots as most people resume their sedentary life-styles. Some but not all memory T cells mimic this cyclic action. Clark et al. now exploit this difference to successfully treat cutaneous T cell lymphoma (CTCL) without increasing patients’ risk of infection.

CTCL is a cancer of skin-homing T cells that can either be restricted to the skin—mycosis fungoides (MF)—or extend to the blood—leukemic CTCL (L-CTCL). MF and L-CTCL are caused by malignancies in two different types of memory T cells: skin resident effector memory T cells (TEM) and central memory T cells (TCM), respectively. Clark et al. found that treating patients with a low dose of alemtuzumab—a monoclonal antibody to CD52, a protein found on the surface of some mature lymphocytes—has a therapeutic effect on L-CTCL but not MF. Indeed, alemtuzumab depleted all T cells, both benign and malignant, from the blood; however, in the skin, only TCM were depleted with alemtuzumab treatment. This effect depended on the presence of neutrophils—phagocytic cells found in the blood but rare in normal skin—which suggests that TCM but not TEM recirculate in the blood. Importantly, the remaining skin resident TEM in the L-CTCL patients may have a protective function, because risk of infection was not heightened in the treated patients. Thus, alemtuzumab destroys the more active malignant cells while sparing the more sessile population, resulting in cancer therapy with retained immunity and, hopefully, the chance for these patients to break many more New Year’s resolutions.