Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model
<b>Background:</b> Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating advanced cancers, their therapeutic success remains limited for many patients, with initial responders often experiencing resistance and relapse. Interleukin-12 (IL-12) is a powerful cy...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Antibodies |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4468/13/4/94 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846106183884079104 |
|---|---|
| author | Fentian Chen Kexin Wu Shiqi Lin Jinlong Cui Xiaoqing Chen Zhiren Zeng Na Yuan Mujin Fang Xue Liu Yuanzhi Chen Wenxin Luo |
| author_facet | Fentian Chen Kexin Wu Shiqi Lin Jinlong Cui Xiaoqing Chen Zhiren Zeng Na Yuan Mujin Fang Xue Liu Yuanzhi Chen Wenxin Luo |
| author_sort | Fentian Chen |
| collection | DOAJ |
| description | <b>Background:</b> Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating advanced cancers, their therapeutic success remains limited for many patients, with initial responders often experiencing resistance and relapse. Interleukin-12 (IL-12) is a powerful cytokine for antitumor immunotherapy, enhancing both lymphocyte recruitment into tumors and immune cell activation. <b>Methods:</b> In this study, we successfully produced mouse interleukin-12 (mIL12) through eukaryotic recombinant expression. In vivo, mIL12 exhibited significant control of tumor immunity in ICI-resistant and aggressive tumor models. Further mechanistic analysis indicated that treatment with mIL12 led to a substantial increase in tumor-infiltrating CD4<sup>+</sup> T, CD8<sup>+</sup> T, cDC1, and CD103<sup>+</sup> cDC1 cells. <b>Results:</b> Our data underscore the potential of a combined therapeutic strategy involving IL-12 with PD-1 and CTLA-4 blockade to elicit a potent antitumor immune response. Notably, the co-administration of mIL12 and PD-1 blockade significantly enhanced the presence of central memory T cells (T<sub>CM</sub>) within tumors. <b>Conclusions:</b> This study is the first to provide evidence that the combination of mIL12 and PD-1 blockers promotes the generation of T<sub>CM</sub>, potentially contributing to a robust and durable antitumor effect. |
| format | Article |
| id | doaj-art-187f0d8991e3408a9a5946c2212ffe3c |
| institution | Kabale University |
| issn | 2073-4468 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj-art-187f0d8991e3408a9a5946c2212ffe3c2024-12-27T14:06:31ZengMDPI AGAntibodies2073-44682024-11-011349410.3390/antib13040094Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer ModelFentian Chen0Kexin Wu1Shiqi Lin2Jinlong Cui3Xiaoqing Chen4Zhiren Zeng5Na Yuan6Mujin Fang7Xue Liu8Yuanzhi Chen9Wenxin Luo10State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health and School of Life Sciences, Xiamen University, Xiamen 361102, China<b>Background:</b> Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating advanced cancers, their therapeutic success remains limited for many patients, with initial responders often experiencing resistance and relapse. Interleukin-12 (IL-12) is a powerful cytokine for antitumor immunotherapy, enhancing both lymphocyte recruitment into tumors and immune cell activation. <b>Methods:</b> In this study, we successfully produced mouse interleukin-12 (mIL12) through eukaryotic recombinant expression. In vivo, mIL12 exhibited significant control of tumor immunity in ICI-resistant and aggressive tumor models. Further mechanistic analysis indicated that treatment with mIL12 led to a substantial increase in tumor-infiltrating CD4<sup>+</sup> T, CD8<sup>+</sup> T, cDC1, and CD103<sup>+</sup> cDC1 cells. <b>Results:</b> Our data underscore the potential of a combined therapeutic strategy involving IL-12 with PD-1 and CTLA-4 blockade to elicit a potent antitumor immune response. Notably, the co-administration of mIL12 and PD-1 blockade significantly enhanced the presence of central memory T cells (T<sub>CM</sub>) within tumors. <b>Conclusions:</b> This study is the first to provide evidence that the combination of mIL12 and PD-1 blockers promotes the generation of T<sub>CM</sub>, potentially contributing to a robust and durable antitumor effect.https://www.mdpi.com/2073-4468/13/4/94immune checkpointinterleukin-12PD-1CTLA-4central memory T cell |
| spellingShingle | Fentian Chen Kexin Wu Shiqi Lin Jinlong Cui Xiaoqing Chen Zhiren Zeng Na Yuan Mujin Fang Xue Liu Yuanzhi Chen Wenxin Luo Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model Antibodies immune checkpoint interleukin-12 PD-1 CTLA-4 central memory T cell |
| title | Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model |
| title_full | Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model |
| title_fullStr | Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model |
| title_full_unstemmed | Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model |
| title_short | Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model |
| title_sort | enhancing tumor immunity with il 12 and pd 1 blockade a strategy for inducing robust central memory t cell responses in resistant cancer model |
| topic | immune checkpoint interleukin-12 PD-1 CTLA-4 central memory T cell |
| url | https://www.mdpi.com/2073-4468/13/4/94 |
| work_keys_str_mv | AT fentianchen enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT kexinwu enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT shiqilin enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT jinlongcui enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT xiaoqingchen enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT zhirenzeng enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT nayuan enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT mujinfang enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT xueliu enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT yuanzhichen enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel AT wenxinluo enhancingtumorimmunitywithil12andpd1blockadeastrategyforinducingrobustcentralmemorytcellresponsesinresistantcancermodel |