适应性免疫抑制对肿瘤病毒治疗影响的多尺度模型
Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer
摘要：
溶瘤病毒疗法-使用特异性杀死肿瘤细胞的病毒-是治疗癌症的创新和非常有前途的途径。然而，其治疗效果主要受到宿主对病毒感染的免疫应答的影响。在目前的工作中，我们提出了一个多尺度数学模型来研究免疫反应如何干扰病毒的溶瘤活性。该模型假设细胞毒性T细胞可以诱导受感染癌细胞的凋亡，并且游离病毒可以通过中和抗体灭活或通过先天免疫应答以恒定速率清除。我们的模拟表明，重新编程肿瘤中的免疫微环境可以显著增强免疫活性宿主中的溶瘤病毒治疗。这种重编程的可行途径是原位病毒介导的CD $8^+$ T细胞运动性损害或阻断B和T淋巴细胞募集。我们的理论结果可以揭示病毒载体的设计或新的协议与整洁的潜在影响的临床实践。
英文摘要：
Oncolytic virotherapy - the use of viruses that specifically kill tumor cells - is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In the present work, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD$8^+$ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.
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