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Updated: Sep 9, 2025
Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
Published on: August 1, 2013
Direct oHSV Infection Induces DC Maturation and a Tumor Therapeutic Response
Doyeon Kim1, Michael Kelly1, Jack Hedberg1,2
1Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
Abstract:
Oncolytic herpes simplex virus (oHSV) is a promising cancer immunotherapy that induces tumor cell lysis and stimulates anti-tumor immunity. Our previous single-cell RNA sequencing analysis of oHSV-treated medulloblastoma tumors revealed expansion and activation of tumor-infiltrating dendritic cells (DCs), and direct oHSV infection of DCs within the brain. While the therapeutic effects of oHSVs have been primarily attributed to tumor cell infection, we hypothesize that direct infection of DCs also contributes to therapeutic efficacy by promoting DC maturation and immune activation. Although the oHSV infection in DCs was abortive, it led to increased expression of major histocompatibility complex (MHC) class I/II and co-stimulatory molecules. oHSV-infected DCs activated naïve CD4+ and CD8+ T cells, inducing expression of CD69 and CD25. These primed T cells exhibited enhanced cytotoxicity against CT-2A glioma cells. Adoptive transfer of oHSV-infected DCs via subcutaneous injection near inguinal lymph nodes delayed tumor growth in a syngeneic CT-2A glioma model, independent of tumor viral replication and lysis. Mechanistically, our in vitro studies demonstrate that oHSV can directly infect and functionally activate DCs, enabling them to prime effective anti-tumor T cell responses. This study highlights the anti-tumor potential of leveraging oHSV-infected DCs to augment viroimmunotherapy as a cancer therapeutic.
Insights
Oncolytic herpes simplex virus (oHSV) directly infects dendritic cells (DCs), enhancing their ability to activate T cells. This oHSV-infected DC immunotherapy effectively delays tumor growth, offering a new cancer treatment strategy.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Oncolytic herpes simplex virus (oHSV) shows promise in cancer immunotherapy by causing tumor cell death and boosting anti-tumor immunity.
- Previous studies indicated oHSV infects dendritic cells (DCs) in medulloblastoma tumors, leading to their activation.
Purpose of the Study:
- To investigate the hypothesis that direct oHSV infection of DCs contributes to therapeutic efficacy by promoting DC maturation and immune activation.
- To explore the potential of using oHSV-infected DCs to enhance viroimmunotherapy for cancer treatment.
Main Methods:
- Single-cell RNA sequencing analysis of oHSV-treated tumors.
- In vitro studies of oHSV infection in DCs.
- Assessment of DC maturation markers (MHC class I/II, co-stimulatory molecules).
- Analysis of T cell activation (CD4+, CD8+, CD69, CD25) and cytotoxicity.
- In vivo studies using adoptive transfer of oHSV-infected DCs in a glioma model.
Main Results:
- oHSV infection, though abortive in DCs, increased MHC class I/II and co-stimulatory molecule expression.
- oHSV-infected DCs activated naïve CD4+ and CD8+ T cells, enhancing their cytotoxicity.
- Adoptive transfer of oHSV-infected DCs delayed tumor growth in a syngeneic glioma model, independent of viral replication in tumors.
Conclusions:
- oHSV can directly infect and functionally activate DCs, leading to effective anti-tumor T cell priming.
- Leveraging oHSV-infected DCs presents a promising strategy to augment viroimmunotherapy for cancer treatment.
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