Factors Affecting Growth Kinetics and Spontaneous Metastasis in the B16F10 Syngeneic Murine Melanoma Model

Fowlkes, Natalie W.; Clemons, Kelli; Rider, Paul J. F.; Subramanian, R.; Wakamatsu, Nobuko; Langohr, Ingeborg M.; Kousoulas, Konstantin G.

doi:10.30802/aalas-cm-18-000036

Cited by 11 publications

(6 citation statements)

References 25 publications

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“…Lung tissue harbors many immune cells, and is a site of metastasis for B16F10 murine 61 and human melanoma. 62 , 63 IC expression changes with age could influence metastatic tumor spread or ICI response there.…”

Section: Resultsmentioning

confidence: 99%

Immune checkpoint expression and relationships to anti‐PD‐L1 immune checkpoint blockade cancer immunotherapy efficacy in aged versus young mice

et al. 2022

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Introduction:Aging is the biggest cancer risk, and immune checkpoint (IC) inhibition (ICI) is a revolutionary cancer immunotherapy approach. Nonetheless, there are limited preclinical/clinical data regarding aging effects on ICI outcomes or age effects on IC expression in different organs or tumors. Methods: Flow cytometry assessed IC on immune and non-immune cells in various organs in young and aged BL6 mice. Comparisons: aged versus young naïve WT versus interferon-γ KO mice and WT challenged with B16F10 melanoma and treated with αPD-1 or αPD-L1 ICI. We co-cultured young and aged T cells and myeloid cells in vitro and used OMIQ analyses to test cell-cell interactions.Results: αPD-1 ICI treated melanoma in young and aged hosts, whereas αPD-L1 ICI was only effective in young. We found considerable, previously undescribed age effects on expression of various IC molecules participating in the ICI treatment, including PD-1, PD-L1, PD-L2, and CD80, in distinct organs and in the tumor. These data help explain differential ICI efficacy in young and aged hosts. Host interferon-γ influenced age effects on IC expression in both directions depending on specific IC molecule and tissue. IC expression was further affected by tumor challenge on immune, non-immune, and tumor cells in tumor and other organs. In in vitro co-culture, αPD-1 versus αPD-L1 distinctly influencedThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Resultsmentioning

confidence: 99%

Immune checkpoint expression and relationships to anti‐PD‐L1 immune checkpoint blockade cancer immunotherapy efficacy in aged versus young mice

et al. 2022

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“…VC2 virus was grown and titrated in Vero cells (ATCC), as described previously (65). and B16F10n-1 cells were engrafted orthotopically in the dermis of the dorsal left dorsal pinna, as previously reported (66). Mice were engrafted with 5×10 5 B16F10n-1 cells in 100 μL PBS.…”

Section: Downloaded Frommentioning

confidence: 99%

Novel Oncolytic Herpes Simplex Virus 1 VC2 Promotes Long-Lasting, Systemic Anti-melanoma Tumor Immune Responses and Increased Survival in an Immunocompetent B16F10-Derived Mouse Melanoma Model

Uche

Fowlkes

et al. 2021

J Virol

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Oncolytic virotherapy (OVT) is now understood to be an immunotherapy that uses viral infection to liberate tumor antigens in an immunogenic context to promote the development of anti-tumor immune responses. The only currently FDA approved oncolytic virotherapy, T-Vec™, is a modified herpes simplex virus type I (HSV-1). While T-Vec™ is associated with limited response rates its modest efficacy supports the continued development of novel OVT viruses. Herein, we test the efficacy of a recombinant HSV-1, VC2, as an OVT in a syngeneic B16F10-derived mouse model of melanoma. VC2 possesses mutations that block its ability to enter neurons via axonal termini. This greatly enhances its safety profile by precluding the virus’s ability to establish latent infection. VC2 has been shown to be a safe, effective vaccine against both HSV-1 and HSV-2 infection in mice, guinea pigs, and non-human primates. We found that VC2 slows tumor growth rates and that VC2 treatment significantly enhances survival of tumor-engrafted, VC2-treated mice over control treatments. VC2-treated mice that survived initial tumor engraftment were resistant to a second engraftment as well as colonization of lungs by intravenous introduction of tumor cells. We found that VC2 treatment induced substantial increases in intratumoral T-cells and a decrease in immunosuppressive T-regulatory cells. This immunity was critically dependent on CD8+ T-cells and less dependent on CD4+ T-cells. Our data provide significant support for the continued development of VC2 as an OVT for the treatment of human and animal cancers. Importance Current oncolytic virotherapies possess limited response rates. However, when certain patient selection criteria are used, oncolytic virotherapy response rates have been shown to increase. This, in addition to the increased response rates of oncolytic virotherapy in combination with other immunotherapies, suggests that oncolytic viruses possess significant therapeutic potential for the treatment of cancer. As such, it is important to continue to develop novel oncolytic viruses as well as support basic research into their mechanisms of efficacy. Our data demonstrate significant clinical potential for VC2, a novel Type 1 oncolytic herpes simplex virus. Additionally, due to the high rates of survival and the dependence on CD8+ T-cells for efficacy, our model will enable study of the immunological correlates of protection for VC2 oncolytic virotherapy and oncolytic virotherapy in general. Understanding the mechanisms of efficacious oncolytic virotherapy will inform the rational design of improved oncolytic virotherapies.

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“…Furthermore, several studies have also suggested that NTP therapy of primary tumors may have an effect at distant, untreated tumor sites. 15 , 53 , 54 While we did not observe any metastatic lesions in any of our tumor‐bearing mice (treated or untreated), more sophisticated models 55 will need to be used to fully evaluate NTP effect on secondary and metastatic tumors. These promising responses to NTP treatment require more detailed studies into not only the underlying mechanisms, but also into how NTP can be controllably dosed to bring about a predictable therapeutic response.…”

Section: Discussionmentioning

confidence: 85%

The effect of local non‐thermal plasma therapy on the cancer‐immunity cycle in a melanoma mouse model

Lin

Backer

Quatannens

et al. 2022

Bioengineering & Transla Med

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Melanoma remains a deadly cancer despite significant advances in immune checkpoint blockade and targeted therapies. The incidence of melanoma is also growing worldwide, which highlights the need for novel treatment options and strategic combination of therapies. Here, we investigate non-thermal plasma (NTP), an ionized gas, as a promising, therapeutic option. In a melanoma mouse model, direct treatment of tumors with NTP results in reduced tumor burden and prolonged survival. Physical characterization of NTP treatment in situ reveals the deposited NTP energy and temperature associated with therapy response, and whole transcriptome analysis of the tumor identified several modulated pathways. NTP treatment also enhances the cancer-immunity cycle, as immune cells in both the tumor and tumor-draining lymph nodes appear more stimulated to perform their anti-cancer functions. Thus, our data suggest that local NTP therapy stimulates systemic, anti-cancer immunity. We discuss, in detail, how these fundamental insights will help direct the translation of NTP technology into the clinic and inform rational combination strategies to address the challenges in melanoma therapy.

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Factors Affecting Growth Kinetics and Spontaneous Metastasis in the B16F10 Syngeneic Murine Melanoma Model

Cited by 11 publications

References 25 publications

Immune checkpoint expression and relationships to anti‐PD‐L1 immune checkpoint blockade cancer immunotherapy efficacy in aged versus young mice

Immune checkpoint expression and relationships to anti‐PD‐L1 immune checkpoint blockade cancer immunotherapy efficacy in aged versus young mice

Novel Oncolytic Herpes Simplex Virus 1 VC2 Promotes Long-Lasting, Systemic Anti-melanoma Tumor Immune Responses and Increased Survival in an Immunocompetent B16F10-Derived Mouse Melanoma Model

The effect of local non‐thermal plasma therapy on the cancer‐immunity cycle in a melanoma mouse model

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