A therapeutic strategy capable of skewing toward a Th1-type immune response is crucial for cancer treatment. Recently, we reported Mycobacterium paragordonae (Mpg) as a potential live vaccine for mycobacterium infections. In this study, we explored the immunotherapeutic potential of heat-killed Mpg (HK-Mpg) in a mouse tumor xenograft model and elucidated its underlying antitumor mechanisms. MC38 cells derived from murine colon adenocarcinoma were implanted by subcutaneously injecting mice. The anticancer effects of HK-Mpg therapy were compared with HK-M. bovis BCG, an effective adjuvant for cancer immunotherapy. HK-Mpg treatment enhanced tumor reduction and mouse survival. Furthermore, HK-Mpg treatment synergistically enhanced the anticancer therapeutic effect of cisplatin. In addition, HK-Mpg enhanced inflammatory cytokine production and recruitment of immune cell into tumor-infiltrating sites and splenocytes in vaccinated mice. Our mechanistic study demonstrates that HK-Mpg therapy elicits a strong antitumor immune response in mice, mainly through natural killer cell-mediated oncolytic activity via the activation of dendritic cells (DCs) and by enhancing inflammatory cytokines production such as IL-12 from DC. Hence, HK-Mpg can be a potential immunotherapy adjuvant, enhancing the effect of cancer chemotherapy.

中文翻译：

---

在异种移植小鼠模型中，热杀死的Paragordonae分枝杆菌疗法通过增强的免疫细胞介导的溶瘤活性来发挥抗癌免疫反应。

能够偏向Th1型免疫应答的治疗策略对于癌症治疗至关重要。最近，我们报道了Paragordonae分枝杆菌（Mpg）作为分枝杆菌感染的潜在活疫苗。在这项研究中，我们探讨了热杀死的Mpg（HK-Mpg）在小鼠肿瘤异种移植模型中的免疫治疗潜力，并阐明了其潜在的抗肿瘤机制。通过皮下注射小鼠植入源自鼠结肠腺癌的MC38细胞。将HK-Mpg治疗的抗癌作用与HK-M进行了比较。bovis BCG，一种有效的癌症免疫治疗佐剂。HK-Mpg治疗可提高肿瘤减少率和小鼠存活率。此外，HK-Mpg治疗协同增强了顺铂的抗癌治疗作用。此外，HK-Mpg增强了炎症细胞因子的产生，并将免疫细胞募集到接种疫苗的小鼠的肿瘤浸润部位和脾细胞中。我们的机理研究表明，HK-Mpg疗法主要通过激活树突状细胞（DC）激活自然杀伤细胞介导的溶瘤活性，并增强炎症性细胞因子的产生，例如DC产生的IL-12，从而在小鼠中引起强烈的抗肿瘤免疫反应。因此，HK-Mpg可以作为潜在的免疫治疗佐剂，增强癌症化学疗法的效果。主要是通过树突状细胞（DC）的激活和增强炎症性细胞因子的产生（例如来自DC的IL-12），通过自然杀伤细胞介导的溶瘤活性来实现的。因此，HK-Mpg可以作为潜在的免疫治疗佐剂，增强癌症化学疗法的效果。主要是通过树突状细胞（DC）的激活和增强炎症性细胞因子的产生（例如来自DC的IL-12），通过自然杀伤细胞介导的溶瘤活性来实现的。因此，HK-Mpg可以作为潜在的免疫治疗佐剂，增强癌症化学疗法的效果。