Poor Prognosis and Therapeutic Responses in LILRB1-Expressing M2 Macrophages-Enriched Gastric Cancer Patients

Immunosuppressive molecules are valuable prognostic biomarkers across different cancer types. Leukocyte immunoglobulin like receptor subfamily B1 (LILRB1) is considered to be an immunosuppressive molecule, which is an important receptor of human leukocyte antigen G. However, the clinical significance of LILRB1 expression in gastric cancer remains unexplored. We analyzed the immunohistochemistry data of 166 gastric cancer patients to determine the clinicopathologic and survival significance of LILRB1. Immunofluorescence was conducted to detect the co-localization of LILRB1 with infiltrating immune cells. Additionally, we also assessed the immune contexture, immune cell functions and tumor microenvironment state related to LILRB1. We found that LILRB1 was mainly present in tumor stroma which was higher in tumor tissues compared with matched adjacent tissues. High-LILRB1 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis showed that LILRB1 had a significant positive correlation with M2 tumor-associated macrophages (TAMs) infiltration. Immunofluorescence confirmed that M2 TAMs were the primary immune cells expressing LILRB1. Dense infiltration of LILRB1+ M2 TAMs yielded an immunosuppressive microenvironment manifested as enriched exhausted CD8+ T cells and increased immunosuppressive cytokines. Moreover, patients with high infiltration of both LILRB1+ cells and M2 TAMs indicated poor prognosis and inferior therapeutic responsiveness to adjuvant chemotherapy. In conclusion, LILRB1+ M2 TAMs were associated with a pro-tumor immune contexture and determine poor prognosis in gastric cancer. Further studies are essential to explore therapeutic targeting LILRB1+ M2 TAMs.

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High plasma levels of COL10A1 are associated with advanced tumor stage in gastric cancer patients

World Journal of Gastroenterology ◽

10.3748/wjg.v26.i22.3024 ◽

2020 ◽

Vol 26 (22) ◽

pp. 3024-3033 ◽

Cited By ~ 1

Author(s):

Laura Necula ◽

Lilia Matei ◽

Denisa Dragu ◽

Ioana Pitica ◽

Ana Iulia Neagu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Plasma Levels ◽

Tumor Stage ◽

High Plasma ◽

Advanced Tumor Stage ◽

Advanced Tumor ◽

Gastric Cancer Patients

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Infiltration Patterns of Immune Cells in Gastric Cancer and Their Clinical Correlation with Prognosis

10.21203/rs.3.rs-18120/v1 ◽

2020 ◽

Author(s):

XiaoLi Wu ◽

Hongbo Ma ◽

YanYan Li

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Mast Cells ◽

Nk Cells ◽

Cancer Patients ◽

Cd8 T Cells ◽

Immune Cells ◽

Immune Cell ◽

M1 Macrophages ◽

Gastric Cancer Patients

Abstract Abstract: Objective Gastric cancer is a malignant tumour that severely affects the health of patients. This study analyses the correlation between gastric cancer-infiltrating immune cell patterns and clinical prognosis and provides a scientific basis for the development of comprehensive tumour prevention and treatment strategies. Method Transcripts and related clinical data from 9-2019 for gastric cancer were downloaded from the TCGA database. The proportions of 22 kinds of immune cells were calculated by CIBERSORT software, and the correlation of each immune cell component ratio with tumour grade, clinical stage and overall survival (OS) was evaluated. Results A total of 413 gene transcript data sets were obtained from the TCGA database, including 381 for gastric cancer and 32 for normal tissues. The expression of various macrophages in tumour tissues was abundant. The immune cell composition, which included resting dendritic cells (p=0.02), M1 macrophages (p=0.031), resting mast cells (p=0.02), CD8 T cells (p=2.445e-04), M0 macrophages (p=6.353e-04), activated mast cells (p=0.006), neutrophils (p=0.003), resting NK cells (p=0.014), and gamma delta T cells (p=0.033), is related to the pathological grade. As the tumour stage of gastric cancer patients progresses, the proportion of some immune cells, including eosinophils (p=0.013), activated mast cells (p=0.042), neutrophils (p=0.007), and resting NK cells (p=0.036) gradually increases, while the proportion of other immune cells, for example, CD8 T cells (p=0.018), Tregs (p=0.039), M1 macrophages (p=0.018), and activated NK cells (p=0.042) gradually decreases. Higher expression of CD8 T cells suggests a better prognosis. Conclusion The composition of tumour-infiltrating immune cells differed greatly in different pathological grades and stages of gastric cancer. CD8 T cells can be used as a prognostic factor for gastric cancer patients.

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Severe Loss of Visceral Fat and Skeletal Muscle After Chemotherapy Predict Poor Prognosis in Metastatic Gastric Cancer Patients Without Gastrectomy

SSRN Electronic Journal ◽

10.2139/ssrn.3391371 ◽

2019 ◽

Author(s):

Wanjing Feng ◽

Mingzhu Huang ◽

Xiaoying Zhao ◽

Siyuan Chen ◽

Chenchen Wang ◽

...

Keyword(s):

Gastric Cancer ◽

Skeletal Muscle ◽

Cancer Patients ◽

Visceral Fat ◽

Poor Prognosis ◽

Metastatic Gastric Cancer ◽

Severe Loss ◽

Gastric Cancer Patients

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Low FAT4 expression is associated with a poor prognosis in gastric cancer patients

Oncotarget ◽

10.18632/oncotarget.23702 ◽

2017 ◽

Vol 9 (4) ◽

pp. 5137-5154 ◽

Cited By ~ 3

Author(s):

Xiaoting Jiang ◽

Zhengchuang Liu ◽

Yingjie Xia ◽

Jungang Luo ◽

Ji Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Poor Prognosis ◽

Gastric Cancer Patients

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HOXB7 overexpression promotes cell proliferation and correlates with poor prognosis in gastric cancer patients by inducing expression of both AKT and MARKs

Oncotarget ◽

10.18632/oncotarget.13604 ◽

2016 ◽

Vol 8 (1) ◽

pp. 1247-1261 ◽

Cited By ~ 14

Author(s):

Xujun He ◽

Zhengchuang Liu ◽

Yingjie Xia ◽

Ji Xu ◽

Guocai Lv ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Cancer Patients ◽

Poor Prognosis ◽

Gastric Cancer Patients

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ILDR1 Is a Prognostic Biomarker and Associated With Immune Inﬁltration in Gastric Cancer

10.21203/rs.3.rs-944596/v1 ◽

2021 ◽

Author(s):

Yanling Ma ◽

WenBo Qi ◽

BaoHong Gu ◽

XueMei Li ◽

ZhenYu Yin ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Dendritic Cells ◽

Cancer Patients ◽

Cd8 T Cells ◽

Immune Cells ◽

Copy Number ◽

Sequencing Data ◽

Number Variation ◽

Gastric Cancer Patients

Abstract Objective: To investigate the association between ILDR1 and prognosis and immune infiltration in gastric cancer. Methods: We analyzed the RNA sequencing data of 9736 tumor tissues and 8587 normal tissues in the TCGA and GTEx databases through the GEPIA2 platform. The expression of ILDR1 in gastric cancer and normal gastric mucosa tissues with GEPIA and TIMER. Clinical subgroup analysis was made through Kaplan-Meier analysis. Analyzed the correlation between ILDR1 and VEGFA expression in gastric cancer, through the gene sequencing data of gastric cancer in TCGA. Explored the relationship between ILDR1 methylation and the prognosis of gastric cancer patients through the MethSurv database. The correlation between ILDR1 and immune cells and the correlation of copy number variation were explored through the TIMER database. Results: ILDR1-high GC patients had a lower PFS and OS. High ILDR1 expression was significantly correlated with tumor grade. There was a negative correlation between the ILDR1 expression and the abundances of CD8+ T, Macrophages and DC and etc. The methylation level of ILDR1 is associated with a good prognosis of gastric cancer. ILDR1 copy number variation was correlated with immune cells, IDLR1 arm-loss was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, and arm-duplication was associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. Conclusion: The increased expression of ILDR1 is associated with poor prognosis in patients with gastric cancer. ILDR1 can be used as a novel predictive biomarker to provide a new therapeutic target for gastric cancer patients.

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