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Effect of doxorubicin / cyclophosphamide-based therapy plus IMMUNEPOTENT CRP on the tumor microenvironment in a murine model of triple-negative breast cancer

Silvia Elena Santana Krímskaya

One of the leading causes of death worldwide is cancer. According to the WHO, in 2020 cancer related deaths reached 10 million. Also in 2020, breast cancer became the most frequent type, surpassing lung cancer. Breast cancers are a highly heterogeneous group of pathologies. Triple negative breast cancer (TNBC) is a subtype that lacks estrogen, progesterone, and epidermal growth factor receptors. Meaning that TNBC tumors can grow and metastasize even in the absence of these growth factors stimuli. Cancer progression is dependent on the interaction of tumor cells with their microenvironment and can result in tumor elimination, disease latency, or progression to metastasis. IMMUNEPOTENT CRP (ICRP) is a dialyzable extract of bovine leukocytes. Previous studies have shown that ICRP reduces oxidative stress in murine macrophages via the NF-�B, promotes myelopoiesis in mice treated with the chemotherapeutic agent 5 fluorouracil, induces immunogenic death in a melanoma model, and prevents tumor implantation in a lymphoma model. Based on these properties, we evaluated if ICRP can be used as a tumor microenvironment modifier, potentiating the antitumor effect of a first-line chemotherapy doxorubicin / cyclophosphamide in a murine model of triple negative breast cancer. In this study we evaluated tumor regression, proliferation index, pro-angiogenic factors (VEGF and �-Sma), expression of CTLA-4, PD1 and PD-L1 checkpoints, leukocyte immunophenotype and cytokine profile in situ. Overall, our results indicate that ICRP increases the therapeutic effectiveness of doxorubicin / cyclophosphamide in a murine model of TNBC