Universidad Autónoma de Nuevo León (UANL), Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, P.O. Box 46 "F", 66455, San Nicolás de los Garza, NL, Mexico.
Universidad Autónoma de Nuevo León (UANL), Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, P.O. Box 46 "F", 66455, San Nicolás de los Garza, NL, Mexico.
Biomed Pharmacother. 2020 Jun;126:110062. doi: 10.1016/j.biopha.2020.110062. Epub 2020 Mar 12.
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.
1889 年，史蒂文·佩吉特（Steven Paget）提出了癌细胞需要允许生长的环境才能生长的理论。这个允许的环境被称为肿瘤微环境（TME），如今已经很明显，TME 参与了实体癌肿瘤的进展和对治疗的反应。三阴性乳腺癌是全球女性中最致命的癌症类型之一，化疗仍然是这些患者的标准治疗方法。免疫无能 CRP 是一种具有免疫调节和抗肿瘤特性的牛可透析白细胞提取物。化疗联合 IMMUNEPOTENT CRP 可改善乳腺癌患者的临床参数。在目前的研究中，我们旨在评估多柔比星/环磷酰胺化疗加 IMMUNEPOTENT CRP 对三阴性乳腺癌小鼠模型的抗肿瘤作用及其对肿瘤微环境的影响。我们评估了 CD8、CD4、T 调节细胞、记忆 T 细胞、髓系来源的抑制细胞、CD71、先天效应细胞以及α-SMA、VEGF、CTLA-4、PD-L1、Gal-3、IDO、IL-2、IFN-γ、IL-12、IL-6、MCP-1 和 IL-10 等肿瘤微环境成分的分子。多柔比星/环磷酰胺+ IMMUNEPOTENT CRP 降低了肿瘤体积，延长了生存期，增加了浸润性和系统性 CD8 T 细胞，并减少了肿瘤抑制分子（如 PD-L1、Gal-3 和 IL-10 等）。总之，我们认为 IMMUNEPOTENT CRP 作为 TME 和免疫反应的调节剂，增强或延长了多柔比星/环磷酰胺在三阴性乳腺癌小鼠模型中的抗肿瘤作用。
