Lighting a Fire in the Tumor Microenvironment Using Oncolytic Immunotherapy

Achard, Catherine; Surendran, Abera; Wedge, Marie-Ève; Ungerechts, Guy; Bell, John C.; Ilkow, Carolina S.

doi:10.1016/j.ebiom.2018.04.020

Cited by 121 publications

(104 citation statements)

References 72 publications

(84 reference statements)

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“…Necrosis can induce an inflammatory response that can further improve the antitumor effect. 21 Therefore, compared with DDP, oHSV2 not only kills tumors directly but also can further stimulate the antitumor immune response to enhance the tumoricidal ability. magnification, Â200).…”

Section: Discussionmentioning

confidence: 99%

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

Zhang

Liang

et al. 2020

Molecular Therapy - Oncolytics

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Oncolytic viruses are promising immunoreagents. Numerous studies have shown that oncolytic virotherapy is effective for many tumors. Herein, we investigated the therapeutic effect of oHSV2, an oncolytic type 2 herpes simplex virus, on mouse colon carcinoma. The in vivo antitumor efficacy of oHSV2 was observed in both unilateral and bilateral colon cancer models. oHSV2 effectively eliminated tumors and prolonged the survival of mice without side effects. Additionally, treatment with oHSV2 effectively prevented the growth of rechallenged tumors and distant implanted tumors. The specific killing ability of splenic immune cells to tumor cells was enhanced. oHSV2 treatment effectively reduced the content of inhibitory immune cells (regulatory T cells [Tregs] and myeloid-derived suppressor cells [MDSCs]) and increased the content of positive immune cells (natural killer [NK], CD8 + T, and dendritic cells [DCs]) in the spleen. Moreover, treatment with oHSV2 remodeled the tumor immune microenvironment. In summary, treatment with oHSV2 can effectively eliminate primary tumors, generate tumor-specific immunity, and elicit immune memory to inhibit tumor recurrence and metastasis. Furthermore, this virotherapy can reshape the immune status of the spleen and tumor microenvironment in mice, which can further improve the therapeutic antitumor effect.

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Section: Discussionmentioning

confidence: 99%

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

Zhang

Liang

et al. 2020

Molecular Therapy - Oncolytics

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“…Clearly larger scale future studies using catheterized urine need to be conducted to accurately evaluate the potentially important role of the bladder microbiome in both bladder cancer pathogenesis/progression and response to immunotherapy agents. ONCOLYTIC VIRUS THERAPY: CONVERTING "IMMUNOLOGICALLY COLD" TUMORS INTO INFLAMED "HOT" TUMORS One intervention capable of dramatically altering the TME immune landscape, is the use of oncolytic or "cancer-killing" viruses (OVs) (32). OVs lead to improved anti-tumor immunity through the induction of both innate and adaptive immune responses, releasing the full range of tumor-associated antigens (TAAs) into an inflammatory environment via tumor lysis and the induction of immunogenic cell death, disrupting the immunosuppressive TME (33)(34)(35)(36).…”

Section: The Urinary Microbiome: a Potential Emerging Factor In The Imentioning

confidence: 99%

Modifying the Non-muscle Invasive Bladder Cancer Immune Microenvironment for Optimal Therapeutic Response

2020

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It is now well-recognized that the tumor microenvironment (TME) is not only a key regulator of cancer progression but also plays a crucial role in cancer treatment responses. Recently, several high-profile publications have demonstrated the importance of particular immune parameters and cell types that dictate responsiveness to immunotherapies. With this increased understanding of TME-mediated therapy, approaches that increase therapeutic efficacy by remodeling the TME are actively being pursued. A classic example of this, in practice by urologists for over 40 years, is the manipulation of the bladder microenvironment for the treatment of non-muscle invasive bladder cancer (NMIBC) by instillation of intravesical bacillus Calmette-Guerin (BCG). The success of BCG treatment is thought to be due to its ability to induce a massive influx of Th1-polarized inflammatory cells, production of Th1 inflammatory cytokines and the generation of tumor-targeted Th1-mediated cytotoxic responses. Whilst BCG immunotherapy is currently the best treatment for NMIBC, ∼30% of patients show no response to this treatment. Here we present a review highlighting a variety of promising alternative immunotherapies being developed that remodel the bladder tumor microenvironment. These include (1) the use of oncolytic viruses which selectively replicate within cancer cells whilst also modifying the immunological components of the TME, (2) manipulation of the bladder microbiome to augment the response to BCG or other immunotherapies (3) utilizing Toll-like Receptor agonists as anti-tumor agents due to their potent stimulation of innate and adaptive immunity and (4) the growing recognition that immunotherapeutic strategies that will have the largest impact on patients may require multiple therapeutic approaches combined together. The accumulating knowledge on TME remodeling holds promise for providing an alternative therapy for patients with BCG-unresponsive NMIBC.

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“…Previous studies have shown that OVs can infect and replicate in CAFs (123) and ECs (124), resulting in their elimination and subsequently increasing immune infiltration in the TME. Most preclinical studies have concluded that OVs have the potential to convert immunologically inert tumors into highly immune-reactive ones and have the ability to attack tumor malignancies in multiple different ways by targeting different subsets of TME cells and disrupting the tumor landscape (125). Indeed, OVs create an acute localized inflammatory response in the tumor that favors immune cell recruitment and activation and results in a therapeutic antitumor effect.…”

Section: Ov-mediated Immunotherapymentioning

confidence: 99%