scholarly journals Immune Cells Expansion From Peripheral Blood of Patients of Three Leading Cancers in Vietnam

2021 ◽  
Vol 37 (3) ◽  
Author(s):  
Chu Thi Thao ◽  
Bui Viet Anh ◽  
Nguyen Van Phong ◽  
Nguyen Trung Kien ◽  
Nguyen Dac Tu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Cell Expansion ◽  
Immune Cell ◽  
Nk Cell ◽  
Ex Vivo ◽  
Cell Number ◽  
Gastric Cancer Patients

Immunotherapy recently attracted the high attention of scientists in cancer treatment. However, this therapy is poorly studied and applied in Vietnam. In this report, we present the results of immune cell ex vivo expansion for cancer treatment. After 20-21 days of culture, the average number of CD3+CD8+ cytotoxic T lymphocytes (CTLs) increased by 633.6-fold, equivalent to 3277.5 × 106 cells, and with the cell viability was 96.3%. Among them, the increasing fold of lung, liver and gastric cancer patients were 232.4, 812.4 and 655.6 respectively. Meanwhile, the average number of CD3-CD56+ NK cells increased by 940.3-fold, equivalent to 2659.3 × 106 cells, with the cell viability of 95%. Gastric cancer patients had the highest fold of Natural killer (NK) cell expansion (1644.9 fold) compared to that in lung cancer (695.0 fold) and liver cancer patients (358.3 fold). These results revealed that our method of immune cell expansion met the requirements in the immune cell number for clinical applications in cancer treatment in Vietnam.

scholarly journals Disruption of Her2-Induced PD-L1 Inhibits Tumor Cell Immune Evasion in Patient-Derived Gastric Cancer Organoids

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6158
Author(s):  
Jayati Chakrabarti ◽  
Vivien Koh ◽  
Nina Steele ◽  
Jennifer Hawkins ◽  
Yoshiaki Ito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Immune Evasion ◽  
Immune Cell ◽  
Suppressor Cells ◽  
Small Subset ◽  
Human Gastric Cancer ◽  
Her2 Positive ◽  
Gastric Cancer Patients

(1) Background: The expression of programmed death-ligand 1 (PD-L1), which interacts with programmed cell death protein 1 (PD-1) on cytotoxic T lymphocytes (CTLs), enables tumors to escape immunosurveillance. The PD-1/PD-L1 interaction results in the inhibition of CTL proliferation, and effector function, thus promoting tumor cell evasion from immunosurveillance and cancer persistence. Despite 40% of gastric cancer patients exhibiting PD-L1 expression, only a small subset of patients responds to immunotherapy. Human epidermal growth factor receptor2 (HER2) is one of the critical regulators of several solid tumors, including metastatic gastric cancer. Although half of PD-L1-positive gastric tumors co-express HER2, crosstalk between HER2 and PD-1/PD-L1 in gastric cancer remains undetermined. (2) Methods: Human gastric cancer organoids (huTGOs) were generated from biopsied or resected tissues and co-cultured with CTLs and myeloid-derived suppressor cells (MDSCs). Digital Spatial Profiling (DSP) was performed on FFPE tissue microarrays of numerous gastric cancer patients to examine the protein expression of immune markers. (3) Results: Knockdown of HER2 in PD-L1/HER2-positive huTGOs led to a concomitant decrease in PD-L1 expression. Similarly, in huTGOs/immune cell co-cultures, PD-L1 expression decreased in huTGOs and was correlated with an increase in CTL proliferation which enhanced huTGO death. Treatment with Nivolumab exhibited similar effects. However, a combinatorial treatment with Mubritinib and Nivolumab was unable to inhibit HER2 expression in co-cultures containing MDSCs. (4) Conclusions: Our study suggested that co-expression of HER2 and PD-L1 may contribute to tumor cell immune evasion. In addition, autologous organoid/immune cell co-cultures can be exploited to effectively screen responses to a combination of anti-HER2 and immunotherapy to tailor treatment for gastric cancer patients.

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

2021 ◽  
Vol 11 ◽  
Author(s):  
Yawei Zhang ◽  
Han Wang ◽  
Xiaoyu Xu ◽  
Huifang Liu ◽  
Tengfei Hao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Advanced Tumor Stage ◽  
Cell Functions ◽  
Advanced Tumor ◽  
Immune Contexture ◽  
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.

scholarly journals Cancer Stem Cell Marker DCLK1 Correlates with Tumorigenic Immune Infiltrates in the Colon and Gastric Adenocarcinoma Microenvironments

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 274 ◽  
Author(s):  
Xiangyan Wu ◽  
Dongfeng Qu ◽  
Nathaniel Weygant ◽  
Jun Peng ◽  
Courtney W. Houchen
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Unmet Need ◽  
The Cancer Genome Atlas ◽  
Stem Cell Marker ◽  
Sequencing Data ◽  
Gastric Cancer Patients

Immunotherapy that has proven efficacy in several solid cancers plays a partial role in improving clinical outcomes of advanced gastrointestinal (GI) cancers. There is an unmet need to find new immune-related therapeutic targets. Doublecortin-like kinase 1 (DCLK1) marks tuft cells which are recognized as cancer-initiating cells and regulators of the type II immune response, and has been studied for its role in many cancers including colon and gastric cancers, but its role in tumor immunity remains unexplored. In the current study, we analyzed colon and gastric cancer RNA sequencing data from 283 and 415 patients, respectively, from The Cancer Genome Atlas (TCGA). High DCLK1 expression predicted the worse clinical outcomes in colon and gastric cancer patients and correlated with increased immune and stromal components. Further analysis indicated that DCLK1 was strongly linked to infiltration of multiple immune cell types, especially TAMs and Treg, and strongly correlated with increased CD8+ T cell inhibitors TGFB1 and CXCL12 and their receptors, suggesting it may contribute to TAM-mediated inhibition of CD8+ T cells. Interestingly, we found that DCLK1 was a prognostic biomarker in left-sided colon cancer, which has worse outcomes and demonstrates a reduced response to existing immunotherapies. In conclusion, our results demonstrate that DCLK1 is linked with functional regulation of the tumor microenvironment and may have potential as a prognostic biomarker and adjuvant target to promote immunotherapy sensitivity in colon and gastric cancer patients.

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

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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