Cegielska Agnieszka, Lisowska Katarzyna A, Dębska-Ślizień Alicja, Imko-Walczuk Beata, Okuniewska Aleksandra, Rutkowski Bolesław
Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland.
Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland.
Postepy Dermatol Alergol. 2018 Oct;35(5):474-480. doi: 10.5114/ada.2018.77237. Epub 2018 Jul 19.
Immunosuppressive therapy, necessary for graft survival, has its clinical consequences with an increased risk of developing malignancies being one of them. It seems that the maintenance of a proper balance between cytotoxic and regulatory activity of the immune system may prevent graft rejection, and with a lower risk of cancer.
To assess the quantitative changes in regulatory T cells (Tregs) in peripheral blood of kidney transplant recipients with post-transplantation skin neoplasm after conversion to mTOR inhibitors (mTORi) and to assess the incidence of secondary skin cancer in that group of patients.
Fourteen patients with post-transplant cutaneous malignancies converted to mTORi were included into the study. The control group consisted of eighteen patients maintained on immunosuppressive regimens without mTORi. The level of Tregs with a phenotype defined as CD4lowCD25high was measured before, and 6 months after, mTORi introduction.
In all cases, 6 months after conversion, a significant decrease in the ratio of CD4CD25 to CD4CD25 from 6.52 to 4.29 was detected ( = 0.035). One patient converted to mTORi developed subsequent skin cancer, while in the control group, subsequent skin cancer was recognized in eight patients. Moreover, introducing mTORi significantly improved progression-free survival in this group of patients ( = 0.016).
Introducing mTORi to the immunosuppressive regimen resulted in an increase in the number of regulatory cells without increasing the incidence of secondary skin cancer in the investigated group of patients.
免疫抑制疗法是移植物存活所必需的,但它具有临床后果,其中患恶性肿瘤的风险增加就是其中之一。免疫系统的细胞毒性和调节活性之间保持适当平衡似乎可以预防移植物排斥,同时降低患癌风险。
评估转换为mTOR抑制剂(mTORi)后肾移植受者外周血中调节性T细胞(Tregs)的定量变化,并评估该组患者继发性皮肤癌的发生率。
本研究纳入了14例转换为mTORi的移植后皮肤恶性肿瘤患者。对照组由18例维持免疫抑制方案但未使用mTORi的患者组成。在引入mTORi之前和之后6个月测量表型定义为CD4lowCD25high的Tregs水平。
在所有病例中,转换后6个月,检测到CD4CD25与CD4CD25的比率从6.52显著下降至4.29(P = 0.035)。1例转换为mTORi的患者发生了继发性皮肤癌,而在对照组中,有八名患者被诊断出患有继发性皮肤癌。此外,引入mTORi显著改善了该组患者的无进展生存期(P = 0.016)。
在免疫抑制方案中引入mTORi导致调节细胞数量增加,而在所研究的患者组中未增加继发性皮肤癌的发生率。