Combination of macrophage inflammatory protein 1 alpha with existing therapies to enhance the antitumor effects on murine hepatoma

Abstract

Existing therapies such as irradiation or sorafenib have limited success in the treatment of hepatocellular carcinoma (HCC) due to tumor recurrence and metastasis. Therefore, combination with other therapeutics is often considered. Macrophage inflammatory protein-1 alpha (MIP-1α) is a member of a family of chemoattractant cytokines that can induce the migration of monocytes, which in turn can play a role in fighting tumors. This study investigated whether intravenous injection of MIP-1α in conjunction with irradiation or sorafenib could enhance the antitumor effects on murine hepatoma. An HCa-I tumor was grown on the right thigh of each C3H/HeN mouse. Mice were then treated with 10 Gy of irradiation, sorafenib, or a combination of MIP-1α with either irradiation or sorafenib, and antitumor and antimetastatic effects were then investigated. To understand the mechanisms, changes in the level of immunological markers were also evaluated. Combination treatment of MIP-1α with irradiation or sorafenib resulted in a significant enhancement of antitumor effects, prevention of lung metastasis and increase in host survival. This was achieved by significantly increasing the levels of the immunological markers: Cluster Differentiation (CD) 8, CD107A and CD11C. We conclude that a combination treatment of MIP-1α with irradiation or sorafenib would be a useful strategy for management of hepatoma.

Analysis of potential biomarkers of response to IL-12 therapy

“…44 While there is literature suggesting MIP-1α may also play a role in tumor cell migration, its proimmune effects may be dominant in the context of IL-12 administration. In support of this idea, Jeong et al 45 found that combining i.v. MIP-1α therapy with preestablished methods of treatment for hepatocellular carcinoma, such as irradiation or sorafenib, significantly enhanced antitumor immunity dependent on increased CD8 + , CD107A + , and CD11C + cells.…”

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq

“…They are located on human chromosome 17 and encode the macrophage inflammatory proteins-1α (MIP-1α) and human CC ligand 3-like protein 1 (CCL3L1), respectively, which belong to the family of chemotactic cytokines known as chemokines. MIP-1α is produced by macrophages and has the ability to induce the migration of monocytes, which then differentiate into dendritic cells (DCs) to recognize an antigen and activate tumor-specific T-cell responses via their potent antigen-presenting capacity to efficiently recognize and kill stem-like cancer cells [ 21 – 26 ]. When the level of MIP-1α decreases, the antitumor activity will be weakened resulting in promoting tumor metastasis.…”

“…CCL3 encoded the macrophage inflammatory proteins-1α (MIP-1α), which was produced by macrophages and had the ability to induce the migration of monocytes. Then the monocytes differentiated into dendritic cells (DCs) to recognize an antigen and activate tumor-specific T-cell responses via their potent antigen-presenting capacity to efficiently recognize and kill stem-like cancer cells [ 21 – 26 ]. The second one could promote tumor metastasis.…”

Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma

“…This stimulates TNF-α and IL-6 production and an inflammatory response [ 125 ]. In murine models, lung metastasis was reportedly prevented and survival improved when irradiation was delivered with intravenously administered recombinant macrophage inflammatory protein-1 alpha (MIP-1α) [ 126 ]. Further research is required to determine the effect of RT on TAMs in the TME.…”