GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model

• DOI: 10.1007/s00262-023-03538-9
• Publication Date: 2023-09-22T05:01:45Z
• Authors: Juan A. Hernández...; Jacquelynne Cerva...; Diana Torres-García; Francisco J. Zuñi...; Osiris J. Patiño-...; Jorge A. Peña Agu...; José Eduardo Agua...; Yonathan Garfias; Laura Montero-León; Laura Romero-Romero; Armando Pérez-Torres; Gladis Fragoso; Edda Sciutto
• Keywords: Triple-negative breast cancer

Abstract Breast cancer is the leading malignancy in women worldwide, both terms of incidence and mortality. Triple-negative breast (TNBC) type with worst clinical outcomes fewer therapeutic options than other types cancer. GK-1 a peptide that experimental model metastatic 4T1 has demonstrated anti-tumor anti-metastatic properties. Herein, (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth number lung macro-metastases but also lymph nodes micro-metastases. Histological analysis reveals reduced 57% intra-tumor vascular areas, diminished leukemoid reaction's progression, spleens' weight length. A significant reduction VEGF-C, SDF-1, angiopoietin-2, endothelin-1 angiogenic factors was induced. Moreover, prevents T cell exhaustion tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It increased IFN-γ granzyme-B expression cytotoxic activity CD8 + TILs cells against cells. All these features were found to be associated better antitumor response prognosis. Altogether, results reinforce potential improve outcome triple-negative immunotherapy. Translation research ongoing towards its evaluation humans.