scholarly journals Characterization of the Immune Cell Infiltration Profile in Pancreatic Carcinoma to Aid in Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
De Luo ◽  
Fei Kuang ◽  
Juan Du ◽  
Mengjia Zhou ◽  
Fangyi Peng ◽  
...  
Keyword(s):  
Pancreatic Carcinoma ◽  
Immune Cell ◽  
Principal Component ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Large Patient ◽  
Mutation Burden ◽  
Large Patient Population ◽  
Cell Cycle Pathway

The tumor microenvironment (TME) is comprised of tumor cells, infiltrating immune cells, and stroma. Multiple reports suggest that the immune cell infiltration (ICI) in TME is strongly associated with responsiveness to immunotherapy and prognosis of certain cancers. Thus far, the ICI profile of pancreatic carcinoma (PC) remains unclear. Here, we employed two algorithms to characterize the ICI profile of PC patients. Based on our results, we identified 2 ICI patterns and calculated the ICI score by using principal component analysis. Furthermore, we revealed that patients with low ICI scores had a better prognosis, compared to high ICI scores. Moreover, we discovered that a low tumor mutation burden (TMB) offered better overall survival (OS), relative to high TMB. In this study, a high ICI score referred to elevated PD-L1/TGF-β levels, increased activation of cell cycle pathway and DNA repair pathway, as well as reduced expression of immune-activation-related genes. We also demonstrated that three metabolic pathways were suppressed in the low ICI score group. These data may explain why a high ICI score equates to a poor prognosis. Based on our analysis, the ICI score can be used as an effective predictor of PC prognosis. Hence, establishing an ICI profile, based on a large patient population, will not only enhance our knowledge of TME but also aid in the development of immunotherapies specific to PC.

scholarly journals Characterization of the Immune Cell Infiltration Landscape of Thyroid Cancer for Improved Immunotherapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Jing Gong ◽  
Bo Jin ◽  
Liang Shang ◽  
Ning Liu
Keyword(s):  
Thyroid Cancer ◽  
Immune Cell ◽  
Endocrine System ◽  
Principal Component ◽  
Prognostic Indicator ◽  
Cell Infiltration ◽  
Therapeutic Effects ◽  
Immune Cell Infiltration ◽  
Mutation Burden

Within the endocrine system, thyroid cancer (THCA) is the most typical malignant tumor. Tumor-infiltrating immune cells play vital roles in tumor progression, recurrence, metastasis as well as response to immunotherapy. However, THCA’s immune infiltrative landscape is still not clarified. Therefore, we utilized two statistical algorithms to investigate the immune cell infiltration (ICI) landscape of 505 THCA samples and defined three ICI immune subtypes. The ICI scores were calculated using principal-component analysis. Increased tumor mutation burden (TMB) and immune-related signaling pathways were associated to a high ICI score. The high ICI score group indicated a relatively longer overall survival (OS) than the low ICI score group. Most immune checkpoint-related and immune activation-related genes were considerably upregulated in the ICI high group, which indicates stronger immunogenicity and a greater likelihood of benefiting from immunotherapy. In two cohort studies of patients receiving immunotherapy, high-ICI-score group showed notable therapeutic effects and clinical advantages compared to those with lower ICI scores. These results demonstrate that ICI score acts as an effective prognostic indicator and predictor of response to immunotherapy.

scholarly journals Association Between Tumor Mutation Burden and Prognosis in Lower-Grade Glioma: An Exploratory Study 

2021 ◽  
Author(s):  
Di Cao ◽  
Jun Wang ◽  
Yan Lin ◽  
Guangwei Li
Keyword(s):  
Immune Cell ◽  
Differential Expression Analysis ◽  
Cell Infiltration ◽  
Lower Grade ◽  
Immune Cell Infiltration ◽  
Hub Genes ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Lower Grade Glioma ◽  
Genome Atlas

Abstract Background: The therapeutic efficacy of immune checkpoint inhibitor therapy is highly influenced by tumor mutation burden (TMB). The relationship between TMB and prognosis in lower-grade glioma is still unclear. We aimed to explore the relationships and mechanisms between them in lower-grade glioma.Methods: We leveraged somatic mutation data from The Cancer Genome Atlas (TCGA). Clinical cases were divided into high- and low-TMB groups based on the median of TMB. Infiltrating immune cells were analyzed using CIBERSORT and differential expression analysis between the prognostic groups performed. The key genes were identified as intersecting between immune-related genes. Cox regression and survival analysis were performed on the intersecting genes. A total of 7 hub genes were identified. The effect of somatic copy number alterations (SCNA) of the hub genes on immune cell infiltration was analyzed using TIMER, which was used to determine the risk factors and immune infiltration status in LGG. Subsequently, based on hub genes, a TMB Prognosis Index (TMBPI) model was constructed to predict the risk in LGG patients. Besides, this model was validated using data from TCGA and Chinese Glioma Genome Atlas (CGGA).Results: High-TMB favored worse prognosis (P＜0.001) and macrophage infiltration was an independent risk factor (P＜0.001). In the high-TMB group (P=0.033, P=0.009), the proportion of macrophages M0 and M2 increased and monocytes decreased (P=0.006). Besides, the SCNA of the hub genes affected the level of immune cell infiltration by varying degrees among which IGF2BP3, NPNT, and PLA2G2A had a significant impact. The AUC of the ROC curve at 1-, 3- and 5-years were all above 0.74.Conclusions: This study implies that high-TMB correlated with unfavorable prognosis in lower-grade glioma. And high-TMB may have an impact on prognosis by changing tumor microenvironment, caused by the SCNAs of genes. The TMBPI model accurately predicted prognosis in LGG patients.

IMMUNOHISTOCHEMICAL CHARACTERIZATION OF IMMUNE CELL INFILTRATION IN PROLIFERATIVE VERRUCOUS LEUKOPLAKIA

2020 ◽  
Vol 130 (3) ◽  
pp. e262-e263
Author(s):  
ANDREIA BUFALINO. MARIEL RUIVO BIANCARDI ◽  
MARIANA PARAVANI PALAÇON ◽  
GABRIELA WALDER CARRASCO ◽  
DARCY FERNANDES ◽  
CAMILA DE OLIVEIRA BARBEIRO ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Proliferative Verrucous Leukoplakia

Stroma and Immune cell infiltration are increased in pancreatic carcinoma after neoadjuvant therapy

Pancreatology ◽  
2018 ◽  
Vol 18 (4) ◽  
pp. S56-S57
Author(s):  
Li Xie ◽  
Leizhou Xia ◽  
Ulla Klaiber ◽  
Milena Sachsenmaier ◽  
Oliver Strobel ◽  
...  
Keyword(s):  
Pancreatic Carcinoma ◽  
Neoadjuvant Therapy ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Molecular Characterization of the Clinical and Tumor Immune Microenvironment Signature of 5-methylcytosine-Related Regulators in non-small Cell Lung Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Taisheng Liu ◽  
Liyi Guo ◽  
Guihong Liu ◽  
Xiaoshan Hu ◽  
Xiaoning Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Check Point ◽  
Clinical Prognosis ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Immune Check Point Inhibitor

Background: DNA methylation is an important epigenetic modification, among which 5-methylcytosine methylation (5mC) is generally associated with tumorigenesis. Nonetheless, the potential roles of 5mC regulators in the tumor microenvironment (TME) remain unclear.Methods: The 5mC modification patterns of 1,374 lung adenocarcinoma samples were analyzed systematically. The correlation between the 5mC modification and tumor microenvironment cell infiltration was further assessed. The 5mCscore was developed to evaluate tumor mutation burden, immune check-point inhibitor response, and the clinical prognosis of individual tumors.Results: Three 5mC modification patterns were established based on the clinical characteristics of 21 5mC regulators. According to the differential expression of 5mC regulators, three distinct 5mC gene cluster were also identified, which showed distinct TME immune cell infiltration patterns and clinical prognoses. The 5mCscore was constructed to evaluate the tumor mutation burden, immune check-point inhibitor response, and prognosis characteristics. We found that patients with a low 5mCscore had significant immune cell infiltration and increased clinical benefit.Conclusion: This study indicated that the 5mC modification is involved in regulating TME infiltration remodeling. Targeting 5mC modification regulators might be a novel strategy to treat lung cancer.

Identification of an Immune-Related Prognostic Signature Associated with Immune Infiltration in Melanoma

2020 ◽  
Author(s):  
Nian Liu ◽  
Zijian Liu ◽  
Xinxin Liu ◽  
Xiaoru Duan ◽  
Yuqiong Huang ◽  
...  
Keyword(s):  
Immune Cell ◽  
Underlying Mechanism ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Prognostic Signature ◽  
Immune Infiltration ◽  
Mutation Burden ◽  
Melanoma Prognosis ◽  
Melanoma Patients ◽  
Immune Related Genes

Abstract Background: Melanoma is the leading cause of cancer-related death among skin tumors, with an increasing incidence worldwide. Few studies have effectively investigated the significance of an immune-related genes (IRGs) signature for melanoma prognosis. Methods: Here, we constructed an IRGs prognostic signature using bioinformatics methods and evaluated and validated its predictive capability. Then, immune cell infiltration and tumor mutation burden (TMB) landscapes associated with this signature in melanoma were analyzed comprehensively. Results: With the 10-IRG prognostic signature, melanoma patients in the low-risk group showed better survival with distinct features of high immune cell infiltration and TMB. Importantly, melanoma patients in this subgroup were significantly responsive to MAGE-A3 in the validation cohort. Conclusions: This immune-related prognostic signature is thus a reliable tool to predict melanoma prognosis; as the underlying mechanism of this signature is associated with immune infiltration and mutation burden, it might reflect the benefit of immunotherapy to patients.

Sign in / Sign up

Export Citation Format

Share Document