Acute inflammation induces immunomodulatory effects on myeloid cells associated with anti-tumor responses in a tumor mouse model

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• 作者：Mohamed L. Salem^a ; ^b ; ^{cecr@unv.tanta.edu.eg" class="auth_mail" title="E-mail the corresponding author} ; ^{mohamed.labib@science.tanta.edu.eg" class="auth_mail" title="E-mail the corresponding author} ; Zeinab I. Attia^c ; Sohaila M. Galal^c
• 关键词：Inflammation ; Anti-tumor ; BCG ; Ehrlich ascite carcinoma ; Poly(I ; C) ; TLR
• 刊名：Journal of Advanced Research
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：7
• 期：2
• 页码：243-253
• 全文大小：2239 K

文摘

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 × 10⁵ 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.