Type I interferons (IFN), especially human IFN alpha (IFNα), have been utilized for antitumor therapy for decades. Human interferon beta (IFNβ) is rarely used for cancer treatment, despite advantages over IFNα in biological activities such as tumor growth inhibition and dendritic cell (DC) activation. The utilization of pegylated human IFNβ (PEG-IFNβ), as monotherapy or in combination with immune checkpoint inhibitors (ICIs) was evaluated in this study through in vivo efficacy studies in syngeneic mouse melanoma, non-small cell lung cancer (NSCLC), and colon adenocarcinoma (COAD) models resistant to immune checkpoint inhibitors (ICIs). In vitro comparative study of PEG-IFNβ and pegylated IFNα-2b was performed in terms of tumor growth inhibition against human melanoma, NSCLC and COAD cell lines and activation of human monocyte-derived DCs (MoDCs). Our data demonstrate that the in vivo antitumor effects of PEG-IFNβ are partially attributable to tumor growth-inhibitory effects and DC-activating activities, superior to pegylated IFNα-2b. Our findings suggest that utilizing PEG-IFNβ as an antitumor therapy can enhance the therapeutic effect of ICIs in ICI-resistant tumors by directly inhibiting tumor growth and induction of DC maturation.

I 型干扰素 (IFN)，尤其是人干扰素α (IFNα)，几十年来一直用于抗肿瘤治疗。尽管人干扰素β (IFNβ) 在肿瘤生长抑制和树突状细胞 (DC) 激活等生物活性方面优于 IFNα，但很少用于癌症治疗。本研究通过对同基因小鼠黑色素瘤、非小细胞肺癌 (NSCLC) 和结肠腺癌（COAD）模型对免疫检查点抑制剂（ICIs）具有抵抗力。PEG-IFNβ和聚乙二醇化IFNα-2b在对人黑色素瘤、NSCLC和COAD细胞系的肿瘤生长抑制以及人单核细胞来源的DC（MoDC）的激活方面进行了体外比较研究。我们的数据表明，PEG-IFNβ的体内抗肿瘤作用部分归因于肿瘤生长抑制作用和DC激活活性，优于聚乙二醇化IFNα-2b。我们的研究结果表明，利用PEG-IFNβ作为抗肿瘤疗法可以通过直接抑制肿瘤生长和诱导DC成熟来增强ICI对ICI耐药肿瘤的治疗效果。