Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Mexico City 14080, Mexico.
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Viruses. 2024 Feb 28;16(3):372. doi: 10.3390/v16030372.
The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.
肿瘤浸润淋巴细胞的缺失会对所有乳腺癌亚型的化疗反应和预后产生负面影响。刺激促炎环境的疗法可能有助于提高对标准治疗的反应，也有助于免疫疗法，如检查点抑制剂。新城疫病毒（NDV）在体外和体内治疗乳腺癌时具有溶瘤活性和免疫调节潜力；然而，其增强乳腺癌肿瘤浸润免疫细胞的潜力尚未得到评估。由于自发性犬乳腺肿瘤代表了人类乳腺癌的转化模型，我们进行了这项概念验证研究，这可为进一步研究 NDV-MLS 作为乳腺癌症的免疫疗法提供依据。六只患有自发性乳腺肿瘤的雌性伴侣犬接受了单次静脉内和肿瘤内注射溶瘤 NDV-MLS。病毒给药后第 6 天，通过组织学和免疫组织化学评估基质、肿瘤内和肿瘤周围区域的免疫细胞浸润。病毒治疗后记录到免疫细胞数量增加，主要在肿瘤周围区域，其中浆细胞和 CD3+和 CD3-/CD79-淋巴细胞占优势。病毒给药耐受性良好，无明显不良反应。这些发现支持进一步研究 NDV-MLS 免疫疗法在乳腺癌症中的应用。
