Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer
Apolipoprotein B mRNA editing enzyme catalytic polypeptide 3B (APOBEC3B) plays an important role in tumor mutagenesis. However, its clinical significance in gastric cancer (GC) remains largely unknown. We enrolled a total of 482 GC patients from Zhongshan Hospital, Fudan University for immunohistoch...
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doaj-ddcff287dcb94d94a69eb5258d18352b2021-09-20T12:43:26ZengTaylor & Francis GroupOncoImmunology2162-402X2021-01-0110110.1080/2162402X.2021.19753861975386Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancerSiyu Xia0Yun Gu1Haijian Zhang2Yuchao Fei3Yifan Cao4Hanji Fang5Jieti Wang6Chao Lin7Heng Zhang8He Li9Hongyong He10Jiejie Xu11Ruochen Li12Hao Liu13Weijuan Zhang14School of Basic Medical Sciences, Fudan UniversityFudan UniversityAffiliated Hospital of Nantong UniversityFudan UniversityZhongshan Hospital, Fudan UniversityFudan UniversityFudan University Shanghai Cancer CenterZhongshan Hospital, Fudan UniversityZhongshan Hospital, Fudan UniversityZhongshan Hospital, Fudan UniversityZhongshan Hospital, Fudan UniversityFudan UniversityZhongshan Hospital, Fudan UniversityZhongshan Hospital, Fudan UniversitySchool of Basic Medical Sciences, Fudan UniversityApolipoprotein B mRNA editing enzyme catalytic polypeptide 3B (APOBEC3B) plays an important role in tumor mutagenesis. However, its clinical significance in gastric cancer (GC) remains largely unknown. We enrolled a total of 482 GC patients from Zhongshan Hospital, Fudan University for immunohistochemistry (IHC) staining to evaluate the prognostic and predictive values of APOBEC3B. Genomic and phenotypic datasets from the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) cohort were downloaded for external validation and complementary bioinformatic analysis. Fresh specimens of additional 60 patients from Zhongshan Hospital, Fudan University were collected to detect CD8+ T cell phenotype with flow cytometry (FCM). The high expression of APOBEC3B indicated inferior overall survival (OS, P < .001 and P = .003) and disease-free survival (DFS, P < .001 and P < .001), yet superior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) in TNM stage II patients. The tumor microenvironment (TME) of APOBEC3B-enriched tumors was characterized by reduced infiltration of tumor reactive CD8+ T cells expressing both effector molecules and immune checkpoints. APOBEC3B high CD8+ T cell high GC patients were most likely to benefit from ACT and PD-1 blockade. Our study demonstrates that APOBEC3B was an independent prognostic and predictive factor in GC. The potential interplay between APOBEC3B and CD8+ T cells merited further investigations.http://dx.doi.org/10.1080/2162402X.2021.1975386apobec3bgastric cancerimmune evasionadjuvant chemotherapyprognosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siyu Xia Yun Gu Haijian Zhang Yuchao Fei Yifan Cao Hanji Fang Jieti Wang Chao Lin Heng Zhang He Li Hongyong He Jiejie Xu Ruochen Li Hao Liu Weijuan Zhang |
spellingShingle |
Siyu Xia Yun Gu Haijian Zhang Yuchao Fei Yifan Cao Hanji Fang Jieti Wang Chao Lin Heng Zhang He Li Hongyong He Jiejie Xu Ruochen Li Hao Liu Weijuan Zhang Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer OncoImmunology apobec3b gastric cancer immune evasion adjuvant chemotherapy prognosis |
author_facet |
Siyu Xia Yun Gu Haijian Zhang Yuchao Fei Yifan Cao Hanji Fang Jieti Wang Chao Lin Heng Zhang He Li Hongyong He Jiejie Xu Ruochen Li Hao Liu Weijuan Zhang |
author_sort |
Siyu Xia |
title |
Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer |
title_short |
Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer |
title_full |
Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer |
title_fullStr |
Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer |
title_full_unstemmed |
Immune inactivation by APOBEC3B enrichment predicts response to chemotherapy and survival in gastric cancer |
title_sort |
immune inactivation by apobec3b enrichment predicts response to chemotherapy and survival in gastric cancer |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2021-01-01 |
description |
Apolipoprotein B mRNA editing enzyme catalytic polypeptide 3B (APOBEC3B) plays an important role in tumor mutagenesis. However, its clinical significance in gastric cancer (GC) remains largely unknown. We enrolled a total of 482 GC patients from Zhongshan Hospital, Fudan University for immunohistochemistry (IHC) staining to evaluate the prognostic and predictive values of APOBEC3B. Genomic and phenotypic datasets from the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) cohort were downloaded for external validation and complementary bioinformatic analysis. Fresh specimens of additional 60 patients from Zhongshan Hospital, Fudan University were collected to detect CD8+ T cell phenotype with flow cytometry (FCM). The high expression of APOBEC3B indicated inferior overall survival (OS, P < .001 and P = .003) and disease-free survival (DFS, P < .001 and P < .001), yet superior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy (ACT) in TNM stage II patients. The tumor microenvironment (TME) of APOBEC3B-enriched tumors was characterized by reduced infiltration of tumor reactive CD8+ T cells expressing both effector molecules and immune checkpoints. APOBEC3B high CD8+ T cell high GC patients were most likely to benefit from ACT and PD-1 blockade. Our study demonstrates that APOBEC3B was an independent prognostic and predictive factor in GC. The potential interplay between APOBEC3B and CD8+ T cells merited further investigations. |
topic |
apobec3b gastric cancer immune evasion adjuvant chemotherapy prognosis |
url |
http://dx.doi.org/10.1080/2162402X.2021.1975386 |
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