Sepsis-induced immune dysfunctions are likely to impact on malignant tumor growth. Sequential sepsis-then-cancer models of tumor transplantation in mice recovering from sepsis have shown that the post-septic immunosuppressive environment was able to promote tumor growth. We herein addressed the impact of sepsis on pre-established malignancy in a reverse cancer-then sepsis experimental model. Mice previously inoculated with MCA205 fibrosarcoma cells were subjected to septic challenges by polymicrobial peritonitis induced by cecal ligation and puncture or endotoxinic shock. The anti-tumoral immune response was assessed through the distribution of tumor-infiltrating immune cells, as well as the functions of cytotoxic cells. As compared to sham surgery, polymicrobial sepsis dampened malignant tumor growth in wild-type (WT) mice, but neither in Toll-like receptor 4 (Tlr4)-/- nor in Myd88-/- mice. Similar tumor growth inhibition was observed following a LPS challenge in WT mice, suggesting a regulatory role of Tlr4 in this setting. The low expression of MHC class 1 onto MCA205 cells suggested the involvement of Natural Killer (NK) cells in sepsis-induced tumor inhibition. Septic insults applied to mice with cancer promoted the main anti-tumoral NK functions of IFNγ production and degranulation. The anti-tumoral properties of NK cells obtained from septic mice were exacerbated when cultured with MHC1low MCA205 or YAC-1 cells. These results suggest that sepsis may harbor dual effects on tumor growth depending on the sequential experimental model. When applied in mice with cancer, sepsis prevents tumor growth in a Tlr4-dependent manner by enhancing the anti-tumoral functions of NK cells.

中文翻译：

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脓毒症通过Toll样受体4相关的增强的自然杀伤细胞活性抑制了癌症小鼠的肿瘤生长。

败血症诱导的免疫功能异常可能会影响恶性肿瘤的生长。从脓毒症中恢复的小鼠的顺序脓毒症-癌症-癌症模型显示，脓毒症后的免疫抑制环境能够促进肿瘤的生长。我们在这里解决了败血症对逆向癌症-然后败血症实验模型中预先建立的恶性肿瘤的影响。盲肠结扎，穿刺或内毒素性休克引起的多菌性腹膜炎使先前接种过MCA205纤维肉瘤细胞的小鼠发生败血性感染。通过肿瘤浸润免疫细胞的分布以及细胞毒性细胞的功能来评估抗肿瘤免疫反应。与假手术相比，微生物败血症可抑制野生型（WT）小鼠的恶性肿瘤生长，但在Toll样受体4（Tlr4）-/-和Myd88-/-小鼠中均没有。在WT小鼠中进行LPS攻击后，观察到相似的肿瘤生长抑制，提示Tlr4在这种情况下具有调节作用。MHC 1类在MCA205细胞上的低表达表明自然杀伤（NK）细胞参与败血症诱导的肿瘤抑制。对患有癌症的小鼠进行的败血性刺激促进了IFNγ产生和脱粒的主要抗肿瘤NK功能。当与MHC1low MCA205或YAC-1细胞一起培养时，败血性NK细胞的抗肿瘤特性会加剧。这些结果表明败血症可能对肿瘤的生长具有双重影响，具体取决于顺序实验模型。当用于患有癌症的小鼠时，