Neutralization of IL-1β in combination with conventional chemotherapy improves the outcome of CRC treatment

IL-1 is an upstream cytokine that controls inflammation and promoting immunosuppression in the tumor microenvironment, thus leading to tumor progression. Deficient in IL-1β in mice induces retardation of colorectal cancer development in mice due to decreased angiogenesis and an increase in the immune response. Thus, we applied new therapeutic approaches using anti-IL-1β antibodies in mice that were injected orthotopically with murine colon cancer cells into the cecum. Antibodies were used alone or in combination with standard chemotherapy protocols (FOLFOX). In this model, chemotherapy or its combination with anti-IL-1β antibodies led to a reduction in the size of the local tumor and it was accompanied by inhibition of IL-1α and IL-1β in local tumors. Nevertheless, histological examination revealed a higher number of micrometastases in livers of mice treated with only FOLFOX in comparison to untreated mice or mice that received only anti-IL-1β antibodies. Dramatically reduction of micrometastases was found in mice that got the combination therapy. The appearance of liver macrometastases was observed only in mice treated with FOLFOX alone. The treatment with only FOLFOX induced increased expression and secretion of both IL-1 agonistic molecules and other pro-inflammatory molecules in liver tissues. On the other hand, combination treatment led to a decrease in local and systemic inflammation. It is clear that anti-tumor therapy is complex and varies depending on differences in the microenvironment of local tumors and metastasis. Addition of anti-IL-1β antibodies to standard chemotherapy protocols may be a promising approach in patients with colorectal cancer for prevention of metastases development.