Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci Transl Med 2012 Jan 18;4(117):117ra7
Date
01/21/2012Pubmed ID
22261031Pubmed Central ID
PMC3373186DOI
10.1126/scitranslmed.3003008Scopus ID
2-s2.0-84856072398 (requires institutional sign-in at Scopus site) 290 CitationsAbstract
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 (T(CM)), and mycosis fungoides (MF), a malignancy of skin resident effector memory T cells (T(EM)). 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 T(CM) from skin, but a diverse population of skin resident T(EM) 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 T(CM) were depleted because they recirculate between the blood and the skin, whereas skin resident T(EM) 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 T(EM) 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 T(CM) but sparing the skin resident T(EM) that provide local immune protection of the skin.
Author List
Clark RA, Watanabe R, Teague JE, Schlapbach C, Tawa MC, Adams N, Dorosario AA, Chaney KS, Cutler CS, Leboeuf NR, Carter JB, Fisher DC, Kupper TSAuthor
Keri S. Chaney MD Assistant Professor in the Dermatology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAged, 80 and over
Alemtuzumab
Antibodies, Monoclonal, Humanized
Antigens, CD
Antigens, Neoplasm
Antineoplastic Agents
CD52 Antigen
Female
Glycoproteins
Humans
Immune System
Immunologic Memory
Male
Middle Aged
Mycosis Fungoides
Neutrophils
Phenotype
Skin
T-Lymphocytes
T-Lymphocytes, Cytotoxic
