4.7 Article

Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8+ T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy

期刊

BIOMEDICINES
卷 10, 期 4, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines10040805

关键词

oncolytic vaccinia virus; cancer antigen-specific T cells; stem-like CD8(+) T cells; lymphoid organs; immune checkpoint blockade

资金

  1. SillaJen, Inc.
  2. Basic Science Research Program through the National Research Foundation (NRF) of Korea [NRF2021R1A2C1011920]
  3. BK21 Four Biomedical Science Program, Seoul National University College of Medicine

向作者/读者索取更多资源

Oncolytic virotherapy can enhance tumor-specific T cell responses and decrease immunosuppression, converting cold tumors into hot tumors and leading to response to combination PD-1 treatment. In addition, oncolytic vaccinia virus can induce long-term durable anticancer immunity.
Oncolytic virotherapy has garnered attention as an antigen-agnostic therapeutic cancer vaccine that induces cancer-specific T cell responses without additional antigen loading. As anticancer immune responses are compromised by a lack of antigenicity and chronic immunosuppressive microenvironments, an effective immuno-oncology modality that converts cold tumors into hot tumors is crucial. To evaluate the immune-activating characteristics of oncolytic vaccinia virus (VACV; JX-594, pexastimogene devacirepvec), diverse murine syngeneic cancer models with different tissue types and immune microenvironments were used. Intratumorally administered mJX-594, a murine variant of JX-594, potently increased CD8(+) T cells, including antigen-specific cancer CD8(+) T cells, and decreased immunosuppressive cells irrespective of tissue type or therapeutic efficacy. Remodeling of tumors into inflamed ones by mJX-594 led to a response to combined anti-PD-1 treatment, but not to mJX-594 or anti-PD-1 monotherapy. mJX-594 treatment increased T cell factor 1-positive stem-like T cells among cancer-specific CD8(+) T cells, and anti-PD-1 combination treatment further increased proliferation of these cells, which was important for therapeutic efficacy. The presence of functional cancer-specific CD8(+) T cells in the spleen and bone marrow for an extended period, which proliferated upon encountering cancer antigen-loaded splenic dendritic cells, further indicated that long-term durable anticancer immunity was elicited by oncolytic VACV.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据