Virus-stimulated neutrophils in the tumor microenvironment enhance T cell-mediated anti-tumor immunity

Despite the effectiveness of classic treatments and available diagnostic tools, cancer continues to be a leading world health problem, with devastating cancer-related death rates. Advances in oncolytic virotherapy have shown promise as potentially effective treatment options in the fight against cancer. The poxviruses have many features that make them an attractive platform for the development of oncolytic vectors, with some candidates currently in clinical trials. Here, we report the design and generation of a new oncolytic vector based on the vaccinia virus Western Reserve (WR) strain. We show that the WR-Δ4 virus, with the combined deletion of four specific viral genes that act on metabolic, proliferation, and signaling pathways (A48R, B18R, C11R, and J2R), has effective anti-tumor capabilities in vivo. In WR-Δ4-infected mice, we observed strong viral attenuation, reduced virus dissemination, and efficient tumor cell growth control in the B16F10 syngeneic melanoma model, with enhanced neutrophil migration and activation of tumor antigen-specific immune responses. This approach provides an alternative strategy toward ongoing efforts to develop an optimal oncolytic poxvirus vector.

show abstract

“… 42 , 43 The anti-tumorigenic influence of virus-stimulated neutrophils is also reported in the B16F10 syngeneic tumor model. 44 …”

Section: Discussionmentioning

confidence: 99%

Development of a Safe and Effective Vaccinia Virus Oncolytic Vector WR-Δ4 with a Set of Gene Deletions on Several Viral Pathways

Mejías-Pérez

Carreño-Fuentes

Esteban

2018

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

show abstract

“…Thus, increased TANs in mesenchymal tumors might contribute to the extreme immunosuppressive environment and plausibly mediate immunotherapy resistance. In contrast, Chang et al reported that virus-stimulated neutrophils in the tumor microenvironment increase T cell-mediated antitumor immunity in a mouse model of melanoma [78]. Although TANs are associated with an immunosuppressive environment within the tumor, clear experimental and clinical evidence is lacking to establish the involvement of TANs in immunotherapy outcomes, which is likely context dependent.…”

Section: Immunotherapy Resistancementioning

confidence: 98%

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Khan

Mittal

McGee

et al. 2020

IJMS

View full text Add to dashboard Cite

Recent efforts in brain tumor research have been directed towards the modulation of the immune system for therapeutic interventions. Several human cancers, including gliomas, are infiltrated with immune cell types—including neutrophils and myeloid-derived suppressor cells—that contribute to tumor progression, invasiveness, and treatment resistance. The role of tumor-associated neutrophils and myeloid-derived suppressor cells in cancer biology remains elusive, as these cells can exert a multitude of pro-tumor and antitumor effects. In this review, we provide the current understanding and novel insights on the role of neutrophils and myeloid-derived suppressor cells in glioma progression and treatment resistance, as well as the mechanisms of pleiotropic behaviors in these cells during disease progression, with an emphasis on possible strategies to reprogram these cells towards their antitumor actions.

show abstract

“…This virus, also known as hemagglutinating virus of Japan, is a restricted pathogen in rodents, producing transmissible respiratory tract infections. SV was evaluated in vitro and in vivo as an oncolytic for human cancers, mainly in colon carcinoma, melanoma, and glioblastoma [ 76 , 77 , 78 ]. In one study, SV was evaluated in vivo in six dogs as therapy for mastocytoma.…”

Section: Oncolytic Viruses For Canine Cancer Treatmentmentioning

confidence: 99%

Oncolytic Viruses for Canine Cancer Treatment

Sánchez

Cesarman‐Maus

Amador-Molina

et al. 2018

Cancers

View full text Add to dashboard Cite

Oncolytic virotherapy has been investigated for several decades and is emerging as a plausible biological therapy with several ongoing clinical trials and two viruses are now approved for cancer treatment in humans. The direct cytotoxicity and immune-stimulatory effects make oncolytic viruses an interesting strategy for cancer treatment. In this review, we summarize the results of in vitro and in vivo published studies of oncolytic viruses in different phases of evaluation in dogs, using PubMed and Google scholar as search platforms, without time restrictions (to date). Natural and genetically modified oncolytic viruses were evaluated with some encouraging results. The most studied viruses to date are the reovirus, myxoma virus, and vaccinia, tested mostly in solid tumors such as osteosarcomas, mammary gland tumors, soft tissue sarcomas, and mastocytomas. Although the results are promising, there are issues that need addressing such as ensuring tumor specificity, developing optimal dosing, circumventing preexisting antibodies from previous exposure or the development of antibodies during treatment, and assuring a reasonable safety profile, all of which are required in order to make this approach a successful therapy in dogs.

show abstract

Virus-stimulated neutrophils in the tumor microenvironment enhance T cell-mediated anti-tumor immunity

Cited by 27 publications

References 47 publications

Development of a Safe and Effective Vaccinia Virus Oncolytic Vector WR-Δ4 with a Set of Gene Deletions on Several Viral Pathways

Development of a Safe and Effective Vaccinia Virus Oncolytic Vector WR-Δ4 with a Set of Gene Deletions on Several Viral Pathways

Role of Neutrophils and Myeloid-Derived Suppressor Cells in Glioma Progression and Treatment Resistance

Oncolytic Viruses for Canine Cancer Treatment

Contact Info

Product

Resources

About