Abstract：
OBJECTIVE: Different regimens of low-dose chemotherapy (LDC) are currently being actively developed and introduced into clinical practice. Along with its obvious advantages compared to conventional chemotherapy (low toxicity, prevention of drug resistance), LDC could also stimulate anti-tumor immune responses in a patient by activating effectors of innate and adaptive immunity and diminishing tumor-associated immunosuppression. As non-myeloablative, LDC could be successfully combined with different anti-cancer immunotherapeutic strategies, including immunoregulatory cytokines. Secreted cyclophilin A (CypA) is of particular interest in this respect. Previously, we showed that recombinant human CypA (rhCypA) had pleiotropic immunostimulatory activity and anti-tumor effects. Thus, rhCypA could be potentially proposed as a perspective component of combined therapy with LDC.
METHODS: In this work, we evaluated the anti-tumor effects of rhCypA combined with low doses of cyclophosphamide, doxorubicin, dacarbazine, and paclitaxel in the experimental mouse tumor models of melanoma B16 and lymphoma EL4 in vivo.
RESULTS: Synergic and potentiating effects of rhCypA combined with LDC were shown in these studies. Furthermore, as a monotherapeutic agent and a component of combined chemoimmunotherapy, rhCypA was shown to modulate the immune tumor microenvironment by enhancing tumor infiltration with macrophages, NK cells, and T cells. It was also found that rhCypA stimulated both systemic and local anti-tumor immune responses.
CONCLUSIONS: RhCypA could be potentially proposed as a perspective component of the combined cancer chemoimmunotherapy.
METHODS: In this work, we evaluated the anti-tumor effects of rhCypA combined with low doses of cyclophosphamide, doxorubicin, dacarbazine, and paclitaxel in the experimental mouse tumor models of melanoma B16 and lymphoma EL4 in vivo.
RESULTS: Synergic and potentiating effects of rhCypA combined with LDC were shown in these studies. Furthermore, as a monotherapeutic agent and a component of combined chemoimmunotherapy, rhCypA was shown to modulate the immune tumor microenvironment by enhancing tumor infiltration with macrophages, NK cells, and T cells. It was also found that rhCypA stimulated both systemic and local anti-tumor immune responses.
CONCLUSIONS: RhCypA could be potentially proposed as a perspective component of the combined cancer chemoimmunotherapy.
摘要：
目的：目前正在积极开发不同的低剂量化疗方案，并将其引入临床实践。与常规化疗相比具有明显的优势（低毒性，预防耐药性)，LDC还可以通过激活先天和适应性免疫的效应子并减少肿瘤相关的免疫抑制来刺激患者的抗肿瘤免疫应答。作为非清髓性的，LDC可以成功地与不同的抗癌免疫治疗策略相结合，包括免疫调节细胞因子。分泌的亲环蛋白A(CypA)在这方面是特别令人感兴趣的。以前,我们表明重组人CypA（rhCypA）具有多效免疫刺激活性和抗肿瘤作用。因此，rhCypA可能被提议作为与LDC联合治疗的透视组成部分。
方法：在这项工作中，我们评估了rhCypA联合低剂量环磷酰胺的抗肿瘤作用，阿霉素,达卡巴嗪,和紫杉醇在小鼠黑色素瘤B16和淋巴瘤EL4的体内实验性肿瘤模型中的作用。
结果：这些研究显示了rhCypA与LDC的协同和增强作用。此外，作为单一治疗剂和联合化学免疫疗法的组成部分，显示rhCypA通过增强巨噬细胞的肿瘤浸润来调节免疫肿瘤微环境，NK细胞,和T细胞。还发现rhCypA刺激全身和局部抗肿瘤免疫应答。
结论：RhCypA可能被提议作为联合癌症化学免疫疗法的一个观点组成部分。
方法：在这项工作中，我们评估了rhCypA联合低剂量环磷酰胺的抗肿瘤作用，阿霉素,达卡巴嗪,和紫杉醇在小鼠黑色素瘤B16和淋巴瘤EL4的体内实验性肿瘤模型中的作用。
结果：这些研究显示了rhCypA与LDC的协同和增强作用。此外，作为单一治疗剂和联合化学免疫疗法的组成部分，显示rhCypA通过增强巨噬细胞的肿瘤浸润来调节免疫肿瘤微环境，NK细胞,和T细胞。还发现rhCypA刺激全身和局部抗肿瘤免疫应答。
结论：RhCypA可能被提议作为联合癌症化学免疫疗法的一个观点组成部分。
