Doxorubicin (DXR) has been reported to have direct cytotoxicity against cancer cells and indirect immunotoxicity by modulation of host antitumor immunity. Hence, it may prevent cancer progression by a dual mechanism. Doxil^®, a formulation of DXR encapsulated in polyethylene glycol modified (PEGylated) liposomes, is the most widely used of the clinically approved liposomal anticancer drugs. However, the effect of Doxil^® on host antitumor immunity is not well understood. In this study, Doxil^® efficiently suppressed tumor growth in immunocompetent mice bearing C26 murine colorectal carcinomas, but not in T cell-deficient nude mice, indicating a contribution of T cells to the overall antitumor effect of Doxil^®. In immunocompetent mice, Doxil^® increased major histocompatibility complex (MHC-1) levels in C26 tumors, which may be an indicator of increased immunogenicity of tumor cells, and potentially amplified tumor immunogenicity by decreasing immunosuppressive cells such as regulatory T cells, tumor-associated microphages and myeloid-derived suppressor cells that collectively suppress T cell-mediated antitumor responses. This suggests that encapsulation of DXR into PEGylated liposomes increased the therapeutic efficacy of DXR though effects on host antitumor immunogenicity in addition to direct cytotoxic effects on tumor cells. This report describes the role of host antitumor immunity in the overall therapeutic effects of Doxil^®. Manipulating pharmacokinetics and biodistribution of chemotherapeutic agents with immunomodulatory properties may increase their therapeutic efficacies by amplifying host antitumor immunity in addition to direct cytotoxic effects on tumor cells.

中文翻译：

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佐剂抗肿瘤免疫作用有助于聚乙二醇化脂质体阿霉素（Doxil®）在具有C26肿瘤免疫能力的小鼠中的总体抗肿瘤作用。

据报道，阿霉素（DXR）通过调节宿主抗肿瘤免疫力具有直接针对癌细胞的细胞毒性和间接免疫毒性。因此，它可以通过双重机制防止癌症进展。阿霉素^®，DXR的制剂封装在聚乙二醇修饰（PEG化）的脂质体，是最广泛使用的临床批准的脂质体的抗癌药物。然而，阿霉素脂质体的影响^®主机抗肿瘤免疫力还不是很清楚。在这项研究中，阿霉素脂质体^®有效地抑制肿瘤生长的免疫活性小鼠轴承C26鼠结肠直肠癌，但不是在T细胞缺陷型裸鼠，表明T细胞对阿霉素的整体的抗肿瘤效果贡献^®。在免疫活性小鼠中，阿霉素脂质体^®在C26肿瘤增加主要组织相容性复合体（MHC-1）的水平，这可能是增加的肿瘤细胞的免疫原性的一个指标，并且通过降低免疫细胞例如调节性T细胞的潜在扩增肿瘤免疫原性，肿瘤相关巨噬细胞和髓样来源的抑制细胞共同抑制T细胞介导的抗肿瘤反应。这表明将DXR封装到聚乙二醇化脂质体中可提高DXR的治疗功效，尽管对肿瘤细胞具有直接的细胞毒性作用，但对宿主的抗肿瘤免疫原性也有影响。这份报告描述主机的抗肿瘤免疫中的阿霉素脂质体的整体治疗效果的作用^®。除了具有对肿瘤细胞的直接细胞毒性作用以外，具有免疫调节特性的化学药物的药代动力学和生物分布可通过扩大宿主抗肿瘤免疫力来提高其治疗效果。