Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt; Center of Excellence in Cancer Research, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
Physiology Unit, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
J Adv Res. 2016 Mar;7(2):243-53. doi: 10.1016/j.jare.2015.06.001. Epub 2015 Jun 19.
Given the self nature of cancer, anti-tumor immune response is weak. As such, acute inflammation induced by microbial products can induce signals that result in initiation of an inflammatory cascade that helps activation of immune cells. We aimed to compare the nature and magnitude of acute inflammation induced by toll-like receptor ligands (TLRLs) on the tumor growth and the associated inflammatory immune responses. To induce acute inflammation in tumor-bearing host, CD1 mice were inoculated with intraperitoneal (i.p.) injection of Ehrlich ascites carcinoma (EAC) (5 × 10(5) cells/mouse), and then treated with i.p. injection on day 1, day 7 or days 1 + 7 with: (1) polyinosinic:polycytidylic (poly(I:C)) (TLR3L); (2) Poly-ICLC (clinical grade of TLR3L); (3) Bacillus Calmette Guerin (BCG) (coding for TLR9L); (4) Complete Freund's adjuvant (CFA) (coding for TLR9L); and (5) Incomplete Freund's Adjuvant (IFA). Treatment with poly(I:C), Poly-ICLC, BCG, CFA, or IFA induced anti-tumor activities as measured by 79.1%, 75.94%, 73.94%, 71.88% and 47.75% decreases, respectively in the total number of tumor cells collected 7 days after tumor challenge. Among the tested TLRLs, both poly(I:C) (TLR3L) and BCG (contain TLR9L) showed the highest anti-tumor effects as reflected by the decrease in the number of EAc cells. These effects were associated with a 2-fold increase in the numbers of inflammatory cells expressing the myeloid markers CD11b(+)Ly6G(+), CD11b(+)Ly6G(-), and CD11b(+)Ly6G(-). We concluded that Provision of the proper inflammatory signal with optimally defined magnitude and duration during tumor growth can induce inflammatory immune cells with potent anti-tumor responses without vaccination.
鉴于癌症的自生性，抗肿瘤免疫反应较弱。因此，微生物产物引起的急性炎症可以诱导信号，导致炎症级联的启动，从而帮助免疫细胞的激活。我们旨在比较 Toll 样受体配体 (TLRL) 诱导的肿瘤生长和相关炎症免疫反应的急性炎症的性质和程度。为了在荷瘤宿主中诱导急性炎症，将 CD1 小鼠用腹腔 (i.p.) 注射艾氏腹水癌 (EAC) (5×10(5)个细胞/只) 接种，并在第 1 天、第 7 天或第 1 天+第 7 天用 i.p. 注射以下物质进行治疗：(1)聚肌苷酸：聚胞苷酸 (poly(I:C)) (TLR3L)；(2)Poly-ICLC（TLR3L 的临床级）；(3)卡介苗 (BCG)（编码 TLR9L）；(4)完全弗氏佐剂 (CFA)（编码 TLR9L）；和 (5)不完全弗氏佐剂 (IFA)。用 poly(I:C)、Poly-ICLC、BCG、CFA 或 IFA 治疗分别导致肿瘤细胞总数减少 79.1%、75.94%、73.94%、71.88%和 47.75%，肿瘤挑战后 7 天收集。在测试的 TLRRL 中，poly(I:C) (TLR3L) 和 BCG（含有 TLR9L）都表现出最高的抗肿瘤作用，这反映在 EAc 细胞数量的减少上。这些作用与表达髓样标记物 CD11b(+)Ly6G(+)、CD11b(+)Ly6G(-)和 CD11b(+)Ly6G(-)的炎症细胞数量增加了 2 倍有关。我们得出结论，在肿瘤生长过程中提供适当的炎症信号，其大小和持续时间最佳定义，可以诱导具有强大抗肿瘤反应的炎症免疫细胞，而无需接种疫苗。
