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

Abstract

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.

PDGFR-alpha inhibits melanoma growth via CXCL10/IP-10: a multi-omicsapproach

“…Inflammation appears as one of the most affected function in cells over-expressing PDGFR-alpha (Supplementary Table S5A and S5B). This finding is consistent with previous data showing that the onset of an appropriate inflammatory response may finally exert anti-tumor activity [57]. Figure 8 shows the functional interconnections of different pro-inflammatory factors up-regulated in PDGFR-alpha over-expressing cells, such as IL6 and CXCL8, further suggesting the hypothesis that an inflammatory response may be involved in the observed anti-angiogenesis and anti-melanoma effect of PDGFR-alpha.…”

The cargo protein MAP17 (PDZK1IP1) regulates the immune microenvironment

“…This chronic, or pathological, inflammation is also one of the causes of neoplastic transformation and cancer development [ 9 ]. Indeed, approximately 25% of tumors have an important association with chronic inflammation derived from an infection, especially stomach cancer [ 10 ].…”

TREM-1low is a novel characteristic for tumor-associated macrophages in lung cancer

“…As we known, TREM-1 could amplify the inflammatory response and inhibition of TREM-1 could decrease death in various experimental septic shock models [7–12, 14, 15]. As an amplifier of immune responses, TREM-1 should be considered as an anti-tumor molecule during tumorigenesis and tumor development [23]. However, recent studies demonstrated that TREM-1 might be involved in tumor progress.…”

“…As previously described, TREM-1 is known as a key molecule for the triggering and amplification of inflammatory response to stimulate proinflammatory cytokines secretion [7, 8]. Different from chronic inflammation, excessive inflammatory response should play an anti-tumor role [21–23]. Thus, we want to reveal the expression and functions of TAM-related TREM-1 in tumor microenvironment.…”