Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis.

IF 6.5 2区 医学 Q1 IMMUNOLOGY Oncoimmunology Pub Date : 2024-12-31 Epub Date: 2024-11-17 DOI:10.1080/2162402X.2024.2429846
Léa Bourguignon, Roxann Hétu-Arbour, Tania Charpentier, Marilène Bolduc, Denis Leclerc, Krista M Heinonen, Alain Lamarre
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Abstract

Cancer presents a significant public health concern, particularly in the context of metastatic disease. Surgical removal of primary tumors, while essential, can inadvertently heighten the risk of metastasis. Thus, there is a critical need for innovative neoadjuvant therapies capable of curtailing metastatic progression before or immediately following tumor resection. Addressing this imperative, the papaya mosaic virus nanoparticle (PapMV) has demonstrated potent immunostimulatory capabilities against both viruses and tumors, effectively hindering their proliferation. Our study reveals that PapMV exerts a protective effect against lung metastasis when administered systemically prior to tumor implantation or during the early stages of metastasis in various mouse models of cancer. This anti-tumor effect is initiated by the recruitment of myeloid cells in the lungs. These cells adopt a pro-inflammatory profile, secreting cytokines such as IFN-α, thus fostering a tumor microenvironment inhospitable to tumor progression. Crucially, this protective mechanism hinges on the presence of macrophages before treatment. TLR7 and IFN-I signaling pathways also play pivotal roles in this process. Furthermore, our findings demonstrate that PapMV triggers the activation of the bone marrow emergency response, which accounts for the influx of myeloid cells into the lungs. This study unveils a novel aspect of PapMV's functionality. By bolstering the immune system, PapMV confers robust protection against metastasis at an early stage of disease progression. This discovery holds promise for therapeutic intervention, particularly as a preemptive measure prior to or just after surgical intervention.

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通过紧急骨髓造血预防肺转移瘤的发展。
癌症是一个重大的公共卫生问题,尤其是转移性疾病。手术切除原发肿瘤固然重要,但却可能无意中增加转移的风险。因此,亟需能够在肿瘤切除前或切除后立即遏制转移进展的创新型新辅助疗法。针对这一迫切需要,木瓜马赛克病毒纳米粒子(PapMV)已证明对病毒和肿瘤都具有强大的免疫刺激能力,能有效阻止它们的增殖。我们的研究表明,在各种癌症小鼠模型中,在肿瘤植入前或转移早期阶段全身给药,木瓜马赛克病毒对肺转移具有保护作用。这种抗肿瘤作用是通过肺部髓系细胞的招募开始的。这些细胞具有促炎特性,分泌 IFN-α 等细胞因子,从而形成不利于肿瘤发展的肿瘤微环境。至关重要的是,这种保护机制取决于治疗前巨噬细胞的存在。TLR7 和 IFN-I 信号通路也在这一过程中发挥了关键作用。此外,我们的研究结果表明,PapMV 引发了骨髓应急反应的激活,这也是骨髓细胞涌入肺部的原因。这项研究揭示了 PapMV 功能的一个新方面。通过增强免疫系统,PapMV 能在疾病进展的早期阶段提供强大的保护,防止转移。这一发现为治疗干预带来了希望,尤其是作为手术干预之前或之后的预防措施。
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来源期刊
Oncoimmunology
Oncoimmunology ONCOLOGYIMMUNOLOGY-IMMUNOLOGY
CiteScore
12.50
自引率
2.80%
发文量
276
审稿时长
24 weeks
期刊介绍: OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy. As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology. The journal covers a wide range of topics, including: -Basic and translational studies in immunology of both solid and hematological malignancies -Inflammation, innate and acquired immune responses against cancer -Mechanisms of cancer immunoediting and immune evasion -Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells -Immunological effects of conventional anticancer therapies.
期刊最新文献
FGL2172-220 peptides improve the antitumor effect of HCMV-IE1mut vaccine against glioblastoma by modulating immunosuppressive cells in the tumor microenvironment. HLA class II neoantigen presentation for CD4+ T cell surveillance in HLA class II-negative colorectal cancer. Markers of tumor-associated macrophages and microglia exhibit high intratumoral heterogeneity in human glioblastoma tissue. Estrogen-related differences in antitumor immunity and gut microbiome contribute to sexual dimorphism of colorectal cancer. Systemic administration of a viral nanoparticle neoadjuvant prevents lung metastasis development through emergency myelopoiesis.
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