Departments of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Radiation Oncology, Albert Einstein College of Medicine & Montefiore Medical Center, Bronx, NY, USA.
Sci Rep. 2019 Oct 29;9(1):15516. doi: 10.1038/s41598-019-51332-4.
Focal ablative therapies have been primarily used for local tumor ablation. However, they often fail to impact systemic disease. Here we propose the use of low intensity focused ultrasound (LOFU), a noninvasive, nontoxic, conformal therapy, to deliver acoustic stress to the tumor for immune priming. We demonstrate that LOFU significantly induces expression and cell surface localization of heat shock proteins in murine breast (4T1) and prostate adenocarcinoma (TPSA23) cancer cell lines. In vivo LOFU followed by ablative radiation therapy (RT) results in primary tumor cure, upregulation of a cytotoxic immune response and induction of immunological memory by inhibiting secondary tumor growth upon re-challenge with tumor cells. We, therefore, describe a regimen of a combination therapy with noninvasive, acoustic immune priming and ablative radiation therapy to generate an in situ tumor vaccine, induce CD8+ T cells against tumor-associated antigens and provide a viable oncologic treatment option for solid tumors.
聚焦消融疗法主要用于局部肿瘤消融。然而，它们往往无法影响系统性疾病。在这里，我们提出使用低强度聚焦超声（LOFU），一种非侵入性、无毒、顺应性的治疗方法，将声应力传递到肿瘤以进行免疫启动。我们证明，LOFU 可显著诱导小鼠乳腺癌（4T1）和前列腺腺癌（TPSA23）癌细胞系中热休克蛋白的表达和细胞表面定位。体内 LOFU 后进行消融放射治疗（RT）可导致原发性肿瘤治愈，通过抑制肿瘤细胞再挑战时的次级肿瘤生长，上调细胞毒性免疫反应并诱导免疫记忆。因此，我们描述了一种联合治疗方案，包括非侵入性、声学免疫启动和消融放射治疗，以产生原位肿瘤疫苗，诱导针对肿瘤相关抗原的 CD8+T 细胞，并为实体瘤提供可行的肿瘤治疗选择。
