PT - JOURNAL ARTICLE AU - Clark, Rachael A. AU - Watanabe, Rei AU - Teague, Jessica E. AU - Schlapbach, Christoph AU - Tawa, Marianne C. AU - Adams, Natalie AU - Dorosario, Andrew A. AU - Chaney, Keri S. AU - Cutler, Corey S. AU - LeBoeuf, Nicole R. AU - Carter, Joi B. AU - Fisher, David C. AU - Kupper, Thomas S. TI - Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients AID - 10.1126/scitranslmed.3003008 DP - 2012 Jan 18 TA - Science Translational Medicine PG - 117ra7--117ra7 VI - 4 IP - 117 4099 - 4100 - AB - Cutaneous T cell lymphoma (CTCL) is a cancer of skin-homing T cells with variants that include leukemic CTCL (L-CTCL), a malignancy of central memory T cells (TCM), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (TEM). We report that low-dose alemtuzumab (αCD52) effectively treated patients with refractory L-CTCL but not MF. Alemtuzumab depleted all T cells in blood and depleted both benign and malignant TCM from skin, but a diverse population of skin resident TEM remained in skin after therapy. T cell depletion with alemtuzumab required the presence of neutrophils, a cell type frequent in blood but rare in normal skin. These data suggest that TCM were depleted because they recirculate between the blood and the skin, whereas skin resident TEM were spared because they are sessile and non-recirculating. After alemtuzumab treatment, skin T cells produced lower amounts of interleukin-4 and higher amounts of interferon-γ. Moreover, there was a marked lack of infections in alemtuzumab-treated L-CTCL patients despite the complete absence of T cells in the blood, suggesting that skin resident TEM can protect the skin from pathogens even in the absence of T cell recruitment from the circulation. Together, these data suggest that alemtuzumab may treat refractory L-CTCL without severely compromising the immune response to infection by depleting circulating TCM but sparing the skin resident TEM that provide local immune protection of the skin.