Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy
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, a...
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MDPI AG
2022-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/4/805 |
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| author | Yun-Hui Jeon Namhee Lee Jiyoon Yoo Solchan Won Suk-kyung Shin Kyu-Hwan Kim Jun-Gyu Park Min-Gang Kim Hang-Rae Kim Keunhee Oh Dong-Sup Lee |
| author_facet | Yun-Hui Jeon Namhee Lee Jiyoon Yoo Solchan Won Suk-kyung Shin Kyu-Hwan Kim Jun-Gyu Park Min-Gang Kim Hang-Rae Kim Keunhee Oh Dong-Sup Lee |
| author_sort | Yun-Hui Jeon |
| collection | DOAJ |
| description | 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<sup>+</sup> T cells, including antigen-specific cancer CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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. |
| first_indexed | 2024-03-09T11:07:19Z |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T11:07:19Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-916dff5130984423b539da41c2dc68ce2023-12-01T00:53:36ZengMDPI AGBiomedicines2227-90592022-03-0110480510.3390/biomedicines10040805Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination ImmunotherapyYun-Hui Jeon0Namhee Lee1Jiyoon Yoo2Solchan Won3Suk-kyung Shin4Kyu-Hwan Kim5Jun-Gyu Park6Min-Gang Kim7Hang-Rae Kim8Keunhee Oh9Dong-Sup Lee10Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaSillaJen, Inc. Research Center, Seongnam-si 13493, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaSillaJen, Inc. Research Center, Seongnam-si 13493, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, KoreaOncolytic 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<sup>+</sup> T cells, including antigen-specific cancer CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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.https://www.mdpi.com/2227-9059/10/4/805oncolytic vaccinia viruscancer antigen-specific T cellsstem-like CD8<sup>+</sup> T cellslymphoid organsimmune checkpoint blockade |
| spellingShingle | Yun-Hui Jeon Namhee Lee Jiyoon Yoo Solchan Won Suk-kyung Shin Kyu-Hwan Kim Jun-Gyu Park Min-Gang Kim Hang-Rae Kim Keunhee Oh Dong-Sup Lee Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy Biomedicines oncolytic vaccinia virus cancer antigen-specific T cells stem-like CD8<sup>+</sup> T cells lymphoid organs immune checkpoint blockade |
| title | Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy |
| title_full | Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy |
| title_fullStr | Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy |
| title_full_unstemmed | Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy |
| title_short | Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8<sup>+</sup> T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy |
| title_sort | oncolytic vaccinia virus augments t cell factor 1 positive stem like cd8 sup sup t cells which underlies the efficacy of anti pd 1 combination immunotherapy |
| topic | oncolytic vaccinia virus cancer antigen-specific T cells stem-like CD8<sup>+</sup> T cells lymphoid organs immune checkpoint blockade |
| url | https://www.mdpi.com/2227-9059/10/4/805 |
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