Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma
Antibodies targeting the programmed cell death protein-1 (PD-1) molecule have been reported to hold promising antitumor activities in patients with nasopharyngeal carcinoma (NPC). However, only a small subset of NPC patients benefits from the anti-PD-1 monotherapy and factors that affect the treatme...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.953884/full |
| _version_ | 1828425524708376576 |
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| author | Liqin Xu Liqin Xu Liqin Xu Yuxiang Ma Chao Fang Chao Fang Chao Fang Zhuobing Peng Zhuobing Peng Zhuobing Peng Fangfang Gao Janne Marie Moll Shishang Qin Qichao Yu Qichao Yu Qichao Yu Yong Hou Yong Hou Yong Hou Karsten Kristiansen Karsten Kristiansen Karsten Kristiansen Wenfeng Fang Susanne Brix Susanne Brix Li Zhang |
| author_facet | Liqin Xu Liqin Xu Liqin Xu Yuxiang Ma Chao Fang Chao Fang Chao Fang Zhuobing Peng Zhuobing Peng Zhuobing Peng Fangfang Gao Janne Marie Moll Shishang Qin Qichao Yu Qichao Yu Qichao Yu Yong Hou Yong Hou Yong Hou Karsten Kristiansen Karsten Kristiansen Karsten Kristiansen Wenfeng Fang Susanne Brix Susanne Brix Li Zhang |
| author_sort | Liqin Xu |
| collection | DOAJ |
| description | Antibodies targeting the programmed cell death protein-1 (PD-1) molecule have been reported to hold promising antitumor activities in patients with nasopharyngeal carcinoma (NPC). However, only a small subset of NPC patients benefits from the anti-PD-1 monotherapy and factors that affect the treatment response need further investigation. This study aimed to examine the impact of multiple genetic and environmental factors on outcome of anti-PD-1 immunotherapy by identifying tumor size, tumor mutation burden (TMB) based on whole exon sequencing, human leukocyte antigen class I (HLA-I) homo-/heterozygosity and supertypes, blood Epstein-Barr virus (EBV) DNA load, T cell proportions, and interferon-γ(IFN-γ) levels in a cohort of 57 NPC patients that received Nivolumab or Camrelizumab treatment. Moreover, we profiled the longitudinal changes in gut microbiota composition using shotgun metagenomics sequencing. We observed that high TMB combined with HLA-I heterozygosity was associated with improved clinical outcomes. In agreement with previous studies, we found that patients with higher plasma EBV DNA load showed worse progression-free survival. We found no evidence for an effect of gut bacterial diversity on the treatment response, but identified a higher abundance of seven specific gut bacteria at baseline of non-responders, including Blautia wexlera and Blautia obeum, as well as four other bacteria belonging to the Clostridiales order, and one Erysipelatoclostridium. Combined, this study provides insight into the influence of several genetic and environmental factors on anti-PD-1 immunotherapy responses in NPC patients. |
| first_indexed | 2024-12-10T16:32:09Z |
| format | Article |
| id | doaj.art-9c735f4571e9471cb0345bbecb45a53d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T16:32:09Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-9c735f4571e9471cb0345bbecb45a53d2022-12-22T01:41:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.953884953884Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinomaLiqin Xu0Liqin Xu1Liqin Xu2Yuxiang Ma3Chao Fang4Chao Fang5Chao Fang6Zhuobing Peng7Zhuobing Peng8Zhuobing Peng9Fangfang Gao10Janne Marie Moll11Shishang Qin12Qichao Yu13Qichao Yu14Qichao Yu15Yong Hou16Yong Hou17Yong Hou18Karsten Kristiansen19Karsten Kristiansen20Karsten Kristiansen21Wenfeng Fang22Susanne Brix23Susanne Brix24Li Zhang25BGI-Shenzhen, Shenzhen, ChinaDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkLatvia MGI Tech SIA, Marupe, LatviaState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBGI-Shenzhen, Shenzhen, ChinaChina National GeneBank, BGI-Shenzhen, Shenzhen, ChinaLaboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, DenmarkBGI-Shenzhen, Shenzhen, ChinaChina National GeneBank, BGI-Shenzhen, Shenzhen, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkBGI-Shenzhen, Shenzhen, ChinaBGI-Shenzhen, Shenzhen, ChinaChina National GeneBank, BGI-Shenzhen, Shenzhen, ChinaCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, ChinaBGI-Shenzhen, Shenzhen, ChinaLatvia MGI Tech SIA, Marupe, LatviaChina National GeneBank, BGI-Shenzhen, Shenzhen, ChinaBGI-Shenzhen, Shenzhen, ChinaLaboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, DenmarkInstitute of Metagenomics, Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, DenmarkInstitute of Metagenomics, Qingdao-Europe Advanced Institute for Life Sciences, Qingdao, ChinaState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaAntibodies targeting the programmed cell death protein-1 (PD-1) molecule have been reported to hold promising antitumor activities in patients with nasopharyngeal carcinoma (NPC). However, only a small subset of NPC patients benefits from the anti-PD-1 monotherapy and factors that affect the treatment response need further investigation. This study aimed to examine the impact of multiple genetic and environmental factors on outcome of anti-PD-1 immunotherapy by identifying tumor size, tumor mutation burden (TMB) based on whole exon sequencing, human leukocyte antigen class I (HLA-I) homo-/heterozygosity and supertypes, blood Epstein-Barr virus (EBV) DNA load, T cell proportions, and interferon-γ(IFN-γ) levels in a cohort of 57 NPC patients that received Nivolumab or Camrelizumab treatment. Moreover, we profiled the longitudinal changes in gut microbiota composition using shotgun metagenomics sequencing. We observed that high TMB combined with HLA-I heterozygosity was associated with improved clinical outcomes. In agreement with previous studies, we found that patients with higher plasma EBV DNA load showed worse progression-free survival. We found no evidence for an effect of gut bacterial diversity on the treatment response, but identified a higher abundance of seven specific gut bacteria at baseline of non-responders, including Blautia wexlera and Blautia obeum, as well as four other bacteria belonging to the Clostridiales order, and one Erysipelatoclostridium. Combined, this study provides insight into the influence of several genetic and environmental factors on anti-PD-1 immunotherapy responses in NPC patients.https://www.frontiersin.org/articles/10.3389/fonc.2022.953884/fullNPCimmunotherapyPD-1TMBHLAEBV |
| spellingShingle | Liqin Xu Liqin Xu Liqin Xu Yuxiang Ma Chao Fang Chao Fang Chao Fang Zhuobing Peng Zhuobing Peng Zhuobing Peng Fangfang Gao Janne Marie Moll Shishang Qin Qichao Yu Qichao Yu Qichao Yu Yong Hou Yong Hou Yong Hou Karsten Kristiansen Karsten Kristiansen Karsten Kristiansen Wenfeng Fang Susanne Brix Susanne Brix Li Zhang Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma Frontiers in Oncology NPC immunotherapy PD-1 TMB HLA EBV |
| title | Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma |
| title_full | Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma |
| title_fullStr | Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma |
| title_full_unstemmed | Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma |
| title_short | Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma |
| title_sort | genomic and microbial factors affect the prognosis of anti pd 1 immunotherapy in nasopharyngeal carcinoma |
| topic | NPC immunotherapy PD-1 TMB HLA EBV |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.953884/full |
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