Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System
The gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-08-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/14/17/4083 |
_version_ | 1797496199986544640 |
---|---|
author | Sujeong Kim Yunjae Kim Suro Lee Yulha Kim Byungkwan Jeon Hyerim Kim Hansoo Park |
author_facet | Sujeong Kim Yunjae Kim Suro Lee Yulha Kim Byungkwan Jeon Hyerim Kim Hansoo Park |
author_sort | Sujeong Kim |
collection | DOAJ |
description | The gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor immunity; however, others do not have such an effect or even promote tumor growth. Identifying effective strains that possess antitumor effects is key for developing live biotherapeutic anticancer products. Here, we found that <i>Lactococcus lactis</i> GEN3013 inhibits tumor growth by regulating tumor angiogenesis and directly inducing cancer cell death. Moreover, <i>L. lactis</i> GEN3013 enhanced the therapeutic effects of oxaliplatin and the PD-1 blockade. Comprehensive immune profiling showed that <i>L. lactis</i> GEN3013 augmented cytotoxic immune cell populations, such as CD4<sup>+</sup> T cells, CD8<sup>+</sup> effector T cells, and NK cells in the tumor microenvironment. Our results indicate that <i>L. lactis</i> GEN3013 is a promising candidate for potentiating cancer treatment in combination with current standard therapy. |
first_indexed | 2024-03-10T03:00:17Z |
format | Article |
id | doaj.art-e3a06b41a25b40e5b4db8a49abbc3a86 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T03:00:17Z |
publishDate | 2022-08-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-e3a06b41a25b40e5b4db8a49abbc3a862023-11-23T12:49:34ZengMDPI AGCancers2072-66942022-08-011417408310.3390/cancers14174083Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune SystemSujeong Kim0Yunjae Kim1Suro Lee2Yulha Kim3Byungkwan Jeon4Hyerim Kim5Hansoo Park6Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, KoreaDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, KoreaGenome and Company, Pangyo-ro 255, Bundang-gu, Seoungnam 13486, KoreaGenome and Company, Pangyo-ro 255, Bundang-gu, Seoungnam 13486, KoreaGenome and Company, Pangyo-ro 255, Bundang-gu, Seoungnam 13486, KoreaGenome and Company, Pangyo-ro 255, Bundang-gu, Seoungnam 13486, KoreaDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, KoreaThe gut microbiota is responsible for differential anticancer drug efficacies by modulating the host immune system and the tumor microenvironment. Interestingly, this differential effect is highly strain-specific. For example, certain strains can directly suppress tumor growth and enhance antitumor immunity; however, others do not have such an effect or even promote tumor growth. Identifying effective strains that possess antitumor effects is key for developing live biotherapeutic anticancer products. Here, we found that <i>Lactococcus lactis</i> GEN3013 inhibits tumor growth by regulating tumor angiogenesis and directly inducing cancer cell death. Moreover, <i>L. lactis</i> GEN3013 enhanced the therapeutic effects of oxaliplatin and the PD-1 blockade. Comprehensive immune profiling showed that <i>L. lactis</i> GEN3013 augmented cytotoxic immune cell populations, such as CD4<sup>+</sup> T cells, CD8<sup>+</sup> effector T cells, and NK cells in the tumor microenvironment. Our results indicate that <i>L. lactis</i> GEN3013 is a promising candidate for potentiating cancer treatment in combination with current standard therapy.https://www.mdpi.com/2072-6694/14/17/4083<i>Lactococcus lactis</i>tumor growthimmune systemchemotherapyimmunotherapy |
spellingShingle | Sujeong Kim Yunjae Kim Suro Lee Yulha Kim Byungkwan Jeon Hyerim Kim Hansoo Park Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System Cancers <i>Lactococcus lactis</i> tumor growth immune system chemotherapy immunotherapy |
title | Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System |
title_full | Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System |
title_fullStr | Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System |
title_full_unstemmed | Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System |
title_short | Live Biotherapeutic <i>Lactococcus lactis</i> GEN3013 Enhances Antitumor Efficacy of Cancer Treatment via Modulation of Cancer Progression and Immune System |
title_sort | live biotherapeutic i lactococcus lactis i gen3013 enhances antitumor efficacy of cancer treatment via modulation of cancer progression and immune system |
topic | <i>Lactococcus lactis</i> tumor growth immune system chemotherapy immunotherapy |
url | https://www.mdpi.com/2072-6694/14/17/4083 |
work_keys_str_mv | AT sujeongkim livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem AT yunjaekim livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem AT surolee livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem AT yulhakim livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem AT byungkwanjeon livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem AT hyerimkim livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem AT hansoopark livebiotherapeuticilactococcuslactisigen3013enhancesantitumorefficacyofcancertreatmentviamodulationofcancerprogressionandimmunesystem |