An optimized protocol for patient-derived xenograft in humanized mice to evaluate the role of IL-34 in immunotherapeutic resistance

Han, Nanumi; Jang, Hye Yoon; Hama, Naoki; Kobayashi, Takuto; Otsuka, Ryo; Wada, Haruka; Seino, Ken‐ichiro

doi:10.1016/j.xpro.2021.100460

Cited by 5 publications

(2 citation statements)

References 3 publications

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“…And the CD200 mechanism of overexpression in PBMC‐humanized mouse models was studied in AML stem cells 135 . Another instance is that the PBMC‐PDX model was used to investigate the role of IL‐34 in immunotherapy resistance and to provide an optimized solution from a single unit 136 . These recent studies point to the active role played by the PBMC‐CDX model in deeper mechanisms.…”

Section: Humanized Mouse Modelsmentioning

confidence: 99%

Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Wang,

Li,

Lin

et al. 2023

Anim Models and Exp Med

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Patient‐derived tumor xenograft (PDX) models, a method involving the surgical extraction of tumor tissues from cancer patients and subsequent transplantation into immunodeficient mice, have emerged as a pivotal approach in translational research, particularly in advancing precision medicine. As the first stage of PDX development, the patient‐derived orthotopic xenograft (PDOX) models implant tumor tissue in mice in the corresponding anatomical locations of the patient. The PDOX models have several advantages, including high fidelity to the original tumor, heightened drug sensitivity, and an elevated rate of successful transplantation. However, the PDOX models present significant challenges, requiring advanced surgical techniques and resource‐intensive imaging technologies, which limit its application. And then, the humanized mouse models, as well as the zebrafish models, were developed. Humanized mouse models contain a human immune environment resembling the tumor and immune system interplay. The humanized mouse models are a hot topic in PDX model research. Regarding zebrafish patient‐derived tumor xenografts (zPDX) and patient‐derived organoids (PDO) as promising models for studying cancer and drug discovery, zPDX models are used to transplant tumors into zebrafish as novel personalized medical animal models with the advantage of reducing patient waiting time. PDO models provide a cost‐effective approach for drug testing that replicates the in vivo environment and preserves important tumor‐related information for patients. The present review highlights the functional characteristics of each new phase of PDX and provides insights into the challenges and prospective developments in this rapidly evolving field.

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Section: Humanized Mouse Modelsmentioning

confidence: 99%

Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Wang,

Li,

Lin

et al. 2023

Anim Models and Exp Med

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“…Consistent with its immunosuppressive properties, IL-34 expression in tumors is related to lower cellular frequencies (CD4 + , CD8 + T cells, and M1-biased macrophage) and molecular (various chemokines and cytokines) effector frequencies in the TME ( 11 , 56 ). Using a neutralizing antibody against IL-34 improved ICI’s therapeutic advantages in combinational therapy models involving a patient-derived xenograft model ( 57 ). Therefore, cancer therapy may gain a potentially game-changing new option if IL-34 inhibitors can be used to limit protumorigenic effects and ICI resistance ( Table 1 and Figure 2 ).…”

Section: Il-34 and Icis In Various Cancer Typesmentioning

confidence: 99%

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer

et al. 2023

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Interleukin-34 (IL-34) is a cytokine that is involved in the regulation of immune cells, including macrophages, in the tumor microenvironment (TME). Macrophages are a type of immune cell that can be found in large numbers within the TME and have been shown to have a role in the suppression of immune responses in cancer. This mmune suppression can contribute to cancer development and tumors’ ability to evade the immune system. Immune checkpoint inhibitors (ICIs) are a type of cancer treatment that target proteins on immune cells that act as “checkpoints,” regulating the activity of the immune system. Examples of these proteins include programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). ICIs work by blocking the activity of these proteins, allowing the immune system to mount a stronger response against cancer cells. The combination of IL-34 inhibition with ICIs has been proposed as a potential treatment option for cancer due to the role of IL-34 in the TME and its potential involvement in resistance to ICIs. Inhibiting the activity of IL-34 or targeting its signaling pathways may help to overcome resistance to ICIs and improve the effectiveness of these therapies. This review summarizes the current state of knowledge concerning the involvement of IL-34-mediated regulation of TME and the promotion of ICI resistance. Besides, this work may shed light on whether targeting IL-34 might be exploited as a potential treatment option for cancer patients in the future. However, further research is needed to fully understand the mechanisms underlying the role of IL-34 in TME and to determine the safety and efficacy of this approach in cancer patients.

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Orthotopic model of pancreatic cancer using CD34+ humanized mice and generation of tumor organoids from humanized tumors

Jeong

Park

Lee

et al. 2023

International Immunopharmacology

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An optimized protocol for patient-derived xenograft in humanized mice to evaluate the role of IL-34 in immunotherapeutic resistance

Cited by 5 publications

References 3 publications

Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Progress in building clinically relevant patient‐derived tumor xenograft models for cancer research

Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer

Orthotopic model of pancreatic cancer using CD34+ humanized mice and generation of tumor organoids from humanized tumors

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