Evaluation Of Immune Profiles Research Articles

Prognostic Impact of Tumor-Infiltrating Immune Cells on Efficacy of Neoadjuvant Chemotherapy in Patients with Advanced or Metastatic Ovarian Cancer: A Retrospective Study.

BACKGROUND Tumor-infiltrating immune cells (TIICs) are implicated in the survival of ovarian cancer (OVCA) patients, but their prognostic significance in advanced or metastatic OVCA patients treated with neoadjuvant chemotherapy (NCAT) has not been well documented, particularly in the Chinese population. MATERIAL AND METHODS A total of 31 advanced or metastatic OVCA patients who underwent NACT were included. The density and positive rate of tumor-infiltrating immune cells (TIICs) within cancer cell nests and in cancer stroma were explored. The correlations of pre- or post-NACT TIICs with the efficacy of NACT and the changes in TIIC subpopulation with NACT were examined. RESULTS Compared with patients with partial benefit from NACT, significantly decreased pre-NACT intratumoral CD68⁺CD163⁺ cells (P=0.0043) and increased pre-NACT intratumoral CD56⁺ cells (P=0.038) were observed in patients with benefit. The high level of pre-NACT intratumoral CD68⁺CD163⁻ M1 macrophage (P=0.075) and stromal CD3⁺PD-1⁺ cells (P=0.085) predicated improved progression-free survival, respectively. Increased post-NACT stromal CD68⁺CD163⁻ M1 macrophage (P=0.01), stromal CD8⁺ T cells (P=0.073), and stromal CD8⁺PD-1⁺ cells (P=0.072) were associated with benefit from NACT. Moreover, NACT increased intratumoral CD3⁺ (P=0.031), CD8+ (P=0.031), and CD3⁺CD8⁺ cells (P=0.031). CONCLUSIONS High intratumoral CD68⁺CD163⁻, intratumoral CD56⁺ cells, and stromal CD3⁺PD-1⁺ cells pre-NACT predicted good prognosis. Intratumoral CD3⁺, CD8⁺, and CD3⁺CD8⁺ cells were increased after NACT. Evaluation of immune profiles may help to identify patients who might benefit from NACT and allow us to further stratify advanced or metastatic OVCA patients treated with NACT for disease management.

Ferroptosis-related STEAP3 acts as predictor and regulator in diffuse large B cell lymphoma through immune infiltration.

Diffuse large B cell lymphoma (DLBCL) is a usual-seen hematological malignant tumor possessing molecular and genetic heterogeneity. Ferroptosis induction has been increasingly acknowledged to be an advantageous therapeutic method in tumor treatment by triggering cell death of tumor cells. However, studies on the function of ferroptosis in DLBCL remain scarce, especially the interaction with the tumor immune microenvironment (TIME). The clinical and biological functions of ferroptosis-related genes in DLBCL were still warranted to be explored. A ferroptosis-related risk model was constructed, followed by functional enrichment analyses and evaluation of immune profile. Quantitative real-time PCR, western blotting, and immunohistochemistry were conducted to examine the RNA and protein levels. Dysregulated expression of the major ferroptosis-related genes was found in DLBCL. A prognostic risk model based on 10 ferroptosis-related genes was constructed. The risk score served as an independent prognostic indicator for DLBCL patients in univariate and multivariate Cox regression analysis. Patients with low-risk scores presented a more favorable prognosis. Functional enrichment analysis revealed that immune-related pathways were significantly enriched, and the high-risk group exhibited less immunocyte infiltration, lower immunoscore, and downregulated PD-L1 expression relative to the low-risk group. Two molecular subtypes were determined through consensus clustering of the expression of ferroptosis-related genes. Cluster 1 was relevant to favorable prognosis, higher immunoscore, and elevated PD-L1 expression. More importantly, STEAP3 was screened as a reliable biomarker for DLBCL, and its enhanced expression levels of mRNA and protein were verified in public databases and clinical specimens. Our study demonstrated the crucial role of ferroptosis-related genes including STEAP3 in the TIME of DLBCL and identified promising novel molecular targets for DLBCL treatment.

Construction of a prognostic classifier and prediction of the immune landscape and immunosuppressive molecules in gliomas based on combination of inflammatory response-related genes and angiogenesis-associated genes

Objective:We aimed to combine inflammatory response-related genes (IRRGs) and angiogenesis-associated genes (AAGs) to build a prognostic classifier and to predict immune landscapes and immunosuppressive molecules in gliomas. Introduction: Gliomas, the commonest primary brain tumors, account for about 80% of cancerous tumors in the central nervous system (CNS), featuring rapid progression, high malignancy, and extremely poor prognosis. The induction of inflammatory responses and angiogenesis have been considered to be closely related to tumors. However, there are little publications systematically elaborating on their impacts on gliomas. Methods: We downloaded the data of IRRGs and AAGs from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and retrieved 68 differentially expressed genes (DEGs), of which 13 DEGs pertained to the prognosis of glioma cases. Next, 9 DEGs were screened from the 13 major DEGs with predictive significance and utilized to build a 9-gene signature as a prognostic risk score model (PRSM) with the aid of univariate Cox regression analyses (CRA) and least absolute shrinkage and selection operator (LASSO)-CRA. On this basis, glioma patients fell into high-risk (HR) group and low-risk (LR) group. Later, we implemented Gene Set Enrichment Analysis (GSEA, Gene Set: WP_ANGIOGENESIS) and calculate the scores of cell infiltration and immune-associated function by harnessing single-sample GSEA (ssGSEA). Results: The prognosis was compared between the two groups by introducing Kaplan-Meier (KM) analysis, which yielded that HR group exhibited poorer prognosis. Additionally, the predictive capacity and independent characteristics were proven by the receiver operating characteristic curve (ROC) and multivariate CRA. Further, We took an evaluation of immune profiles, which unraveled that immunosuppressive cell count was distinctively larger in HS group. Finally, a protein-protein interaction (PPI) network of DEGs was built, and 10 hub genes were obtained, of which epidermal growth factor receptor (EGFR) was closely related to poor prognosis. Conclusion: A 9-gene signature was established on the strength of IRRGs and AAGs for predicting glioma prognosis, tumor microenvironment (TME), immune landscapes and immunosuppressive molecules. However, the molecular mechanism developed by this signature to function in tumor immunity needs further experimental research in the future and is expected to be a research target for glioma immunotherapy strategies.

An Evaluation of Immune-Profile and IgE Binding Proteins in the Sera of Respiratory Allergy Patients of North India to Commonly Consumed Foods

An Evaluation of Immune-Profile and IgE Binding Proteins in the Sera of Respiratory Allergy Patients of North India to Commonly Consumed Foods

Evaluation of Immune Profiles and MicroRNA Expression Profiles in Peripheral Blood Mononuclear Cells of Long-Term Stable Liver Transplant Recipients and Recipients With Acute Rejection Episodes

ObjectiveThis study aimed to document the difference of immunophenotypes in peripheral blood mononuclear cells (PBMCs) between long-term stable liver transplant recipients and recipients with acute rejection. We also sought to identify whether there is any correlation between microRNA (miRNA) expression profile and the differential immunoprofile in these 2 groups to establish a specific miRNA biomarker to identify potential liver transplant recipients. MethodsPBMCs were isolated from 53 stable liver transplant recipients (STA group) and 15 liver transplant recipients with repeated biopsy-proven rejection episodes admitted to our hospital. Immunoprofiles were analyzed by means of flow cytometry. Analysis of miRNA expression in the PBMCs was performed by means of real-time polymerase chain reaction. ResultsThe immune profiling analysis showed increased frequency of peripheral natural killer cells and regulatory T cells in stable liver transplant recipients compared with the acute rejection recipients and healthy volunteers (P < .05). There was no significant difference in the immune cell levels (CD19+ B cells, CD4+ T cells, and CD8+ T cells) in PBMCs among the transplant recipient groups and healthy control subjects. Three miRNAs, miR-18b, miR-340, and miR-106b, were up-regulated in the PBMCs of the STA recipients compared with recipients with acute rejection. ConclusionsThese results suggest that miR-18b, miR-340, and miR-106b, which regulate the expression of specific immunophenotypes, can be used as potential biomarkers to identify long-term stable liver transplant recipients from recipients with acute rejection.

Evaluation of Immune Profile in Patients with Multiple Myeloma Using Cytof Technology

Introduction: CyTOF (time-of-flight mass cytometry) is a novel high-dimensional technology which permits immunophenotyping and analysis of signaling in single cells. This approach enables simultaneous evaluation of up to 40 parameters using antibodies tagged with distinct elemental isotopes, by combining flow cytometry with atomic mass spectrometry. Since multiple myeloma (MM) is characterized by immune dysfunction, we used CyTOF technology to define the complex immune profile in MM patient bone marrow (BM) samples.Methods: We used 40 different markers to define various B, T, natural killer (NK) subsets, as well as cells of monocytic, granulocytic, erythroid and platelet lineages. Our preliminary data are results from 10 patients with MGUS/ smoldering MM (SMM); 10 newly diagnosed MM; 20 relapsed/refractory MM; and 15 WM patients (5 newly diagnosed and 10 receiving treatment) in comparison with age-matched healthy donors’ BM (HD). A significantly larger cohort of MM (N=150) and WM (N=50) patients is being similarly analyzed and will be presented. To evaluate phenotypic abnormalities in various B cell subsets, we used B lineage markers CD10, CD19, CD20, CD22, CD27, CD34, CD38, CD45, IgA, IgD, IgG and IgM to define B cells maturation stages from hematopoietic stem cells (HSC) to naïve to mature B lymphocytes (pro-B; pre-B-I; pre-B-II; immature B; and mature (naïve) B cells), as well as memory non-switched and memory switched B cells, plasmablasts, normal (CD138+CD38+CD19+CD45+) and clonal plasma cells (CD138+CD38+CD19-CD45-/low), which reside in the specific BM niche. Furthermore, natural killer (NK) subsets (such as NK and NKT cells) and T cells (such as memory CD4T, naive CD4T, memory CD8T, naive CD8T, T regulatory cells and Tg/d cells) were examined. High-dimensional data was obtained using CyTOF technology and analyzed by SPADE and viSNE software.Results: Our data showed significantly decreased HSC in patients with newly diagnosed and relapsed/refractory MM compared to HD (P<0.025). A significant increase in pre-B-I cells was detected in relapsed/refractory MM vs. MGUS/SMM (P<0.028), but the opposite trend was observed in the pre-B-II subpopulation (P<0.005). No differences in immature B cell populations were observed in different stages of MM. However, a significantly higher percentage of immature B cells was present in relapsed/refractory MM compared to HD (P=0.008), and transitional B cells were significantly decreased in newly diagnosed MM compared to HD (P<0.001). Moreover, memory B cells were significant decreased in all MM stages compared to HD (P<0.003). Non-switched memory B cells were significantly increased in MGUS and SMM compared to newly diagnosed MM, while a significant increase of switched memory B cells was present in newly diagnosed MM compared to relapsed/refractory MM. A significant increase in plasmablasts was seen in relapsed/refractory MM in comparison with other MM stages (P<0.011) by CyTOF analyses. Malignant plasma cells (PC) were defined as CD19-, CD38++, CD45-/dim, CD138+ and either cyk or cyl positive. Importantly, a significant increase in clonal PC was found in all MM stages vs. HD, as well as in newly diagnosed MM compared to relapsed/refractory MM (P<0.01). The percentage of PC from CyTOF analyses correlated with % of PC obtained using flow cytometry by Bland-Altman method comparison. We also observed significant differences in T cell subsets including naïve, central memory, effector, and effector memory CD4+ and CD8+T populations between MGUS and newly diagnosed MM, but no significant changes in T regulatory and Tg/d cells. Furthermore, plasmacytoid dendritic (pDC) cells were significantly increased in newly diagnosed MM, and PD-1 expressed on pDC was significantly decreased in newly diagnosed MM compared to MGUS (P=0.007). Interestingly, PD-1 and its ligand PD-L1 were variably expressed on B cells (2-9% and 3-27%) and PC (0.5-46% and 3-41%) from MM BM samples. Other surface molecules including CD269 (4-32%), CD289 (1-8%), CD362 (0.5-1%) and CD329 (1-4%), were variably expressed in PC.Conclusion: A better understanding of the neoplastic BM milieu will provide the framework for identifying and validating novel targeted therapies directed against MM. CyTOF technology represents a novel diagnostic tool to assess the status not only of MM, but also of host immunity, and may allow for the development of rational personalized therapies. DisclosuresNo relevant conflicts of interest to declare.