一項新的發(fā)表于Sci Transl Med雜志上的研究"Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients"可幫助解釋為什么一種叫做阿侖單抗的藥物對治療罹患某種叫做皮膚T細(xì)胞淋巴瘤或CTCL的瘙癢加疼痛類型的皮膚癌非常有效,。
此外,，阿侖單抗的治療似乎不會增加感染的風(fēng)險——這是一個意外的發(fā)現(xiàn),，因為該藥會殺滅所有的T和B免疫細(xì)胞,，而這些細(xì)胞都是至關(guān)重要的抗感染斗士,。 傳統(tǒng)的觀念預(yù)計,，接受阿侖單抗治療的病人會比感染了HIV的患者的病情更重—HIV也會消滅T細(xì)胞--但這些病人并沒有病情變得更重,。
Rachael Clark及其同事對幾位CTCL病人進(jìn)行觀察之后發(fā)現(xiàn)了其究竟,。 研究人員給病人低劑量的阿侖單抗并觀察到這些患者的病情好轉(zhuǎn)且沒有隨之出現(xiàn)感染,。 接著,，該小組分析了采自那些已完全康復(fù)病人的皮膚樣本并注意到其皮膚中的T細(xì)胞執(zhí)行著監(jiān)控感染的職責(zé)。
與在血液中循環(huán)的T細(xì)胞不同——這些T細(xì)胞會游走到出現(xiàn)問題的部位以保護(hù)身體不受侵犯,，研究人員發(fā)現(xiàn)了非移動性的皮膚T細(xì)胞——這是一組新發(fā)現(xiàn)的固守在某個社區(qū),，在此為皮膚，中的等待麻煩出現(xiàn)的警員,。
原來,，阿侖單抗只殺滅循環(huán)中的T細(xì)胞,，但它不會打擾那些處在皮膚組織中的T細(xì)胞。 由于在這種疾病中的惡性T細(xì)胞是在血液中循環(huán)游走的,，因此該藥可在清除這種疾病的同時讓組織中的免疫記憶保持大體上的完整,，因而防止更多的感染發(fā)生。 （生物谷Bioon.com）
doi: 10.1126/scitranslmed.3003008
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Skin Effector Memory T Cells Do Not Recirculate and Provide Immune Protection in Alemtuzumab-Treated CTCL Patients
Rachael A. Clark1,2,*, Rei Watanabe1,*, Jessica E. Teague1, Christoph Schlapbach1, Marianne C. Tawa2, Natalie Adams2, Andrew A. Dorosario2, Keri S. Chaney1, Corey S. Cutler2, Nicole R. LeBoeuf1, Joi B. Carter3, David C. Fisher2 and Thomas S. Kupper1,2,*
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.
