IMMUNEPOTENT CRP plus doxorubicin/cyclophosphamide chemotherapy remodel the tumor microenvironment in an air pouch triple-negative breast cancer murine model

Abstract

In 1889, Steven Paget postulated the theory that cancer cells require a permissive environment to grow. This permissive environment is known as the tumor microenvironment (TME) and nowadays it is evident that the TME is involved in the progression and response to therapy of solid cancer tumors. Triple-negative breast cancer is one of the most lethal types of cancer for women worldwide and chemotherapy remains the standard treatment for these patients. IMMUNEPOTENT CRP is a bovine dialyzable leukocyte extract with immunomodulatory and antitumor properties. The combination of chemotherapy and IMMUNEPOTENT CRP improves clinical parameters of breast cancer patients. In the current study, we aimed to evaluate the antitumor effect of doxorubicin/cyclophosphamide chemotherapy plus IMMUNEPOTENT CRP and its impact over the tumor microenvironment in a triple-negative breast cancer murine model. We evaluated CD8⁺, CD4⁺, T regulatory cells, memory T cells, myeloid-derived suppressor cells, CD71⁺, innate effector cells and molecules such as α-SMA, VEGF, CTLA-4, PD-L1, Gal-3, IDO, IL-2, IFN-γ, IL-12, IL-6, MCP-1, and IL-10 as part of the components of the TME. Doxorubicin/cyclophosphamide + IMMUNEPOTENT CRP decreased tumor volume, prolonged survival, increased infiltrating and systemic CD8⁺ T cells and decreased tumor suppressor molecules (such as PD-L1, Gal-3, and IL-10 among others). In conclusion, we suggest that IMMUNEPOTENT CRP act as a modifier of the TME and the immune response, potentiating or prolonging anti-tumor effects of doxorubicin/cyclophosphamide in a triple-negative breast cancer murine model.

Keywords: 4T1; Breast cancer; IMMUNEPOTENT CRP (ICRP); Immunotherapy; Treatment; Tumor microenvironment.