Transcriptome Signature of Immune Cells Post Reovirus Treatment in KRAS Mutated Colorectal Cancer

Fogel, Elisha J.; Samouha, Avishai; Goel, Sanjay; Maitra, Radhashree

doi:10.2147/cmar.s324203

Cited by 6 publications

(11 citation statements)

References 48 publications

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“…TNFα-promoted apoptosis of cancer cells can also be induced through CASP9 upregulation through NF-κB and its target miR-1276 [40]. Our original research data showcased the fact that reovirus treatment was able to significantly increase apoptotic activity in KRAS mutated CRC through the heightened expression of CASP8 and CASP9 [11].…”

Section: Reovirus-induced Apoptosis Is Enacted Through the Actions Of...mentioning

confidence: 69%

“…The oligomerization of the APAF1 protein at the onset of apoptosis is triggered by the binding of cytosolic cytochrome c, which prevents the autoinhibition of the APAF1 gene [31]. As indicated by our original research data, reovirus administration effectively promotes the expression of FAM96A and decrease the expression of VEGFB, thus inhibiting cell proliferation and angiogenesis [11].…”

Section: Post-reovirus the Expression Of Vegfb And Fam96a Results In ...mentioning

confidence: 85%

“…The primary purpose of this review is to affirm the antitumorigenic effects of reovirus on various signaling and growth-factor related genetic pathways. As our published paper has shown, and as this review highlights, reovirus-mediated immune modulation results in antitumor activity that is realized via innate and adaptive immune responses [11]. These responses are influenced by the altered expression of genes within vital biological pathways.…”

Section: Introductionmentioning

confidence: 79%

“…In metastatic CRC, this gene is generally upregulated, pointing the cellular proliferation of cancer cells. Our original research data showed that ANGPT1 and NOS3 expression were successfully inhibited post reovirus treatment, lending more evidence to the reduction of cell signaling activity and cancer progression [11].…”

Section: Altered Expression Of Signaling Genes Nos3 and Angpt1 Post R...mentioning

confidence: 87%

“…Specifically, it inhibits cell growth and promotes apoptosis [22]. Our original research data showed that post-reovirus, RTN4 and CHORDC1 expression are significantly upregulated at multiple time points indicating that lymphocytic activity is increased, while tumorigenesis is effectively impeded [11].…”

Section: Discussionmentioning

confidence: 97%

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Oncolytic Virus Affects the RAS Pathway in Cancer: RNA Sequence Analysis

et al. 2021

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Background: Approximately 45% of individuals diagnosed with Colorectal Cancer (CRC) also possess KRAS mutations. One developing therapeutic method for this disease is reovirus treatment. It is theorized that reovirus treatment on patients with KRAS mutated CRC cells would be successful due to the virus' innate oncolytic properties [1]. Reovirus, a stable form of nonenveloped double-stranded RNA, causes minor infections in humans under normal circumstances. However, when the virus encounters KRAS mutated cells, it has the potential to lyse them [2]. While this method of treatment to CRC has shown signs of success, we are still some ways from universal administration of reovirus as a treatment. This review seeks to utilize various studies, as well as our original research data, to investigate reovirus as an efficient method of treatment, with a focus on select growth, apoptotic and RAS-related genes, and their effectiveness of mitigating KRAS mutated CRC post reovirus treatment. Furthermore, the review highlights transcriptome analysis as an effective tool to examine these genes and their activity. It has been shown that reovirus treatment induces apoptosis and mitigates growth related gene activity.Conclusions: This review confirms the novelty of our findings on the efficacy of reovirus in CRC treatment. The study that this review article discusses concluded that 10 apoptotic and lymphocyte-related genes were found to be upregulated and 6 angiogenesis and Ras-related genes were found to be downregulated post reovirus treatment. These findings enforce the notion that reovirus could be used as a novel treatment for KRAS mutated CRC.

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Section: Reovirus-induced Apoptosis Is Enacted Through the Actions Of...mentioning

confidence: 69%

Section: Post-reovirus the Expression Of Vegfb And Fam96a Results In ...mentioning

confidence: 85%

Section: Introductionmentioning

confidence: 79%

Section: Altered Expression Of Signaling Genes Nos3 and Angpt1 Post R...mentioning

confidence: 87%

Section: Discussionmentioning

confidence: 97%

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Oncolytic Virus Affects the RAS Pathway in Cancer: RNA Sequence Analysis

et al. 2021

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Molecular insights and promise of oncolytic virus based immunotherapy

Iyer,

Ravichandran,

Karuppusamy

et al. 2024

Advances in Protein Chemistry and Structural Biology

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Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor by reducing the immunosuppressive tumor microenvironment in a colorectal cancer model

Yari,

Hosseini,

Asiyabi

et al. 2024

Preprint

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Immunotherapy is a type of tumor treatment that increases anti-tumor immunity to inhibit tumor growth. By enhancing the immune response through the lysis of tumor cells with an oncolytic virus and inhibiting the immune system's inhibitory reactions, the effectiveness of immunotherapy can be improved. In this study on a mouse model of colorectal cancer, the efficacy of oncolytic reovirus in a combined treatment with an adenovector expressing carcinoembryonic antigen (CEA) and PD-1/PD-L1 inhibitor was evaluated. The tumorized mice with CEA-expressing CT26 cells were immunized with a constructed adenovector expressing CEA along with PD-1/PD-L1 inhibitor. Then three doses of reovirus were injected into the tumor. On day of 26th, all mice were sacrificed, and tumor size, histopathological findings, and immune response to tumor antigens were compared among treatment groups. The results showed that immunization with CEA, combined with treatment with reovirus and PD-1/PD-L1 inhibitor, resulted in the lowest tumor growth among the treated groups. Additionally, the combined treatment group exhibited the highest level of cytotoxic immunity. This treatment also led to a decrease in Foxp3 in the tumor microenvironment and TNF-α secretion compared to other groups. Furthermore, through the production of IFN-γ and increased cytotoxic effect, it was demonstrated that the cellular immune system works more efficiently. Histopathological evaluations revealed the lowest number of mitosis and the highest amount of tumor-infiltrating lymphocytes (TILs) in this group. In conclusion, although the combination of tumor vaccines with oncolytic viruses improves treatment efficacy, inhibiting the PD-1/PD-L1 interaction can further enhance immunovirotherapy efficacy by reducing immunosuppressive effects boosted by the virus activity, and stimulating the immune system. This approach, in combination with other treatment methods, shows promise in controlling tumor growth.

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Transcriptome Signature of Immune Cells Post Reovirus Treatment in KRAS Mutated Colorectal Cancer

Cited by 6 publications

References 48 publications

Oncolytic Virus Affects the RAS Pathway in Cancer: RNA Sequence Analysis

Oncolytic Virus Affects the RAS Pathway in Cancer: RNA Sequence Analysis

Molecular insights and promise of oncolytic virus based immunotherapy

Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor by reducing the immunosuppressive tumor microenvironment in a colorectal cancer model

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