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Bubble heat map showing the predictive and prognostic value of immune cell-type frequencies in breast cancer of different subtypes (A) and grades (B). The associations between the fractions and OS and DFS were assessed by Cox regression analysis. A blue bubble indicates that a higher fraction of immune cells is associated with decreased DFS or OS; a red bubble indicates that a higher fraction of immune cells is associated with increased DFS or OS. The size of the bubble indicates the statistical significance level.
Source publication
The immune infiltration of tumors is closely related to clinical outcomes. The composition of tumor-infiltrating immune cells (TIICs) can serve as biomarkers for predicting response to treatment and survival in different patient subgroups in terms of chemotherapy and immunotherapy. This study is focused on investigating the clinical implications of...
Contexts in source publication
Context 1
... assess the prognostic values of immune cells, a Cox regression analysis was used to analyze the correlations between survival and the proportions of TIICs. As shown in Figure 4, the sizes of the bubbles in the heatmap represent the level of statistical significance, while blue and red colors indicate a negative and positive correlation, respectively, between TIICs and OS/DFS. In breast cancer patients, a higher proportion of M0 macrophages indicated decreased DFS (HR=1.67, ...
Context 2
... Cl 1.74~22.49, p<0.02) ( Figure 4A). In patients with different stages of cancer, the correlation between TIICs and OS/DFS exhibited large differences ( Figure 4B) ...
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Citations
... The elevation of M0 macrophages in the highrisk cohort can be ascribed to the existence of circulating macrophages within the tumor microenvironment. These macrophages have the potential to modify the tumor microenvironment, consequently fostering tumor progression [52]. Additionally, cancerassociated fibroblasts (CAFs) in invasive breast cancer have been reported to facilitate the induction of monocytes into M2 macrophages [53,54]. ...
... A notable advantage of this approach over traditional pathology lies in its ability to provide richer and more nuanced information about the cellular landscape, including distinctions between subpopulations of epithelial cells and other cells in the TME. While deconvolution of bulk RNA-seq has proven useful in breast cancer and other tumour types in predicting treatment and survival outcomes [18,[21][22][23][24], its accuracy and applicability to predict HIPEC response in HGSOC remains unexplored. ...
... Clinical outcomes are highly connected to the immune infiltration of malignancies [108]. The composition of tumor-infiltrating immune cells (TIICs) may serve as biomarkers for predicting treatment response and survival in various patients subgroups in terms of chemotherapy and immunotherapy [109,110]. ...
Backgrounds
The overall survival of patients with lower-grade gliomas and glioblastoma varies greatly. No reliable or existing procedures can accurately forecast survival and prognostic biomarkers for early diagnosis in glioma and glioblastoma. However, investigations are progressing in immunotherapy, tumor purity, and tumor microenvironment which may be therapeutic targets for glioma and glioblastoma.
Results
This study indicated the possible prognostic signatures that can be used to identify immune-related prognostic biomarkers in the prediction of the survival of low-grade glioma (LGG) patients which may be a possible therapeutic target. In addition, the Kaplan–Meier plot, ESTIMATE algorithm, and TIMER 2.0 analysis indicated that Krüppel-like factor 15 (KLF15) p = 0.030, Aquaporin 7 (AQP7) p = 0.001, and Human 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) p = 0.005 are significantly associated in glioma. Hence, they may be possible prognostic biomarkers in glioma. Meanwhile, in the glioblastoma, only KLF15 has a significant association with glioblastoma ( p = 0.025). Stromal and immune scores of gliomas were determined from transcriptomic profiles of LGG cohort from TCGA (The Cancer Genome Atlas) using the ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumours using Expression data algorithm). The immune infiltration of the KLF15, AQP7, and AGPAT9 for low-grade glioma and glioblastoma was determined using TIMER immune 2.0 which indicates correlation with tumor purity for KLF15, AQP7, and AGPAT9, but only KLF15 and AGPAT9 are significantly associated in both glioma and glioblastoma, respectively.
Conclusions
These results highlight the significance of microenvironment monitoring, analysis of glioma and glioblastoma prognosis, and targeted immunotherapy. To our knowledge, this is the first time to investigate an analysis that revealed that KLF15, AQP7, and AGPAT9 may be important prognostic biomarkers for patients with glioma and KLF15 for patients with glioblastoma. Meanwhile, KLF15 and AGPAT9 are significantly associated in both glioma and glioblastoma, respectively, for tumor purity.
... Neutrophils can either promote cancer progression by enhancing tumor angiogenesis or mediate antibody-dependent cellular cytotoxicity against cancer cells, thus functioning as a double-edged sword [15]. Research suggests that certain subsets of TIICs, such as tumor-infiltrating lymphocytes, hold promise as potential prognostic markers for BC due to considerable lymphocytic infiltration [16]. A promising approach to improving the prognosis of patients with BC involves targeting immune checkpoints (ICPs) PD-L1 and CTLA-4 on T-cell surfaces, which impede tumor growth [17,18]. ...
Background
Cuproptosis, i.e., copper-induced programmed cell death, has potential implications in cancer therapy. However, the impact of the cuproptosis-related gene (CRG) dihydrolipoyl dehydrogenase (DLD) on breast cancer (BC) prognosis remains underexplored.
Methods
We employed real-time quantitative PCR and multiplexed immunostaining techniques to quantify DLD expression in both BC and the adjacent non-cancerous tissues. Immunofluorescence analysis was employed to assess the influence of DLD on immune cells and immunological checkpoints in the BC microenvironment. DLD knockdown experiments were conducted in BC cell lines MDA-MB-468 and SK-BR-3, with knockdown efficiency validated via western blot. Subsequently, we performed the cell counting kit-8 (CCK-8) assay, clone formation assay, Transwell migration assay, and invasion assay. To construct a prognostic model, we employed a Lasso-Cox regression analysis of immune-related genes associated with DLD. Additionally, we established a competing endogenous RNA network based on CRGs to evaluate potential regulatory pathways.
Results
Compared to the adjacent tissues, BC tissues exhibited markedly elevated DLD expression levels. In vitro experiments demonstrated that DLD knockdown effectively inhibited BC cell migration, invasion, and proliferation. DLD exhibited positive correlations with CD68⁺ macrophages and PD-L1 in the tumor, as well as with macrophages and CD4⁺ T cells in the stroma. Tumor regions with high DLD expression were enriched in PD-L1 and macrophages, while stromal regions with high DLD expression contained CD4⁺ T cells and macrophages. The AUC values for 1-, 3-, and 5-year overall survival in TCGA-BRCA training set were 0.67, 0.66, and 0.66, respectively. A nomogram with a C-index of 0.715 indicated that risk score, tumor stage, and age could serve as independent prognostic factors for BC.
Conclusion
Our findings underscore the significant predictive significance of DLD in BC and its influence on the tumor microenvironment. DLD represents a promising diagnostic and prognostic marker for BC, offering novel avenues for the identification of therapeutic targets and the enhancement of immunotherapy in BC.
... The homing behavior of NK cells is mainly dependent on the signal transduction between the homing receptor on the surface and the ligand, while the infiltration of NK cells is influenced by the interaction with TME [77,78]. Studies have found that once NK cells infiltrate tumor cells and homing receptors bind to ligands, immune cell activation signals will be transmitted and secrete perforin, granzyme, and apoptosis-inducing factors [79] to play the anti-tumor immune role of NK cells. ...
The prognosis for cancer patients has declined dramatically in recent years due to the challenges in treating malignant tumors. Tumor immunotherapy, which includes immune target inhibition and chimeric antigen receptor cell treatment, is currently evolving quickly. Among them, natural killer (NK) cells are gradually becoming another preferred cell immunotherapy after T cell immunotherapy due to their unique killing effects in innate and adaptive immunity. NK cell therapy has shown encouraging outcomes in clinical studies; however, there are still some problems, including limited efficacy in solid tumors, inadequate NK cell penetration, and expensive treatment expenses. Noteworthy benefits of nanomaterials include their chemical specificity, biocompatibility, and ease of manufacturing; these make them promising instruments for enhancing NK cell anti-tumor immune responses. Nanomaterials can promote NK cell homing and infiltration, participate in NK cell modification and non-invasive cell tracking and imaging modes, and greatly increase the effectiveness of NK cell immunotherapy. The introduction of NK cell-based immunotherapy research and a more detailed discussion of nanomaterial research in NK cell-based immunotherapy and molecular imaging will be the main topics of this review.
... Recently, the attention of researchers has been focused on the study of the features of the TME of malignant neoplasms of various localizations, including PCa [19][20][21]. In this context, a large array of data has been accumulated on the significance of the infiltration of the PCa tissue by T-cells [22], macrophages [23], MCs [24], as well as on the influence of fibroblasts on the spatial organization of the neoplasm stroma [25,26]. ...
Background. The tumor microenvironment (TME) plays an important role in the occurrence and progression of prostate cancer (PCa). At the same time, the mechanisms and features of the interaction between tumor cells and individual components of the TME in PCa remain not fully elucidated. The aim was to study the expression levels of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p in the PCa tissue and to analyze their relationship with the features of TME. Materials and Methods. The work is based on the analysis of the results of the examination and treatment of 50 patients with PCa of stages II—IV. The expression of miRNA in the PCa tissue was analyzed by the real-time polymerase chain reaction. The expression of alpha-smooth muscle actin (α-SMA), vimentin (VIM), and CD68 in PCa tissue was determined by the immunohistochemical method. The identification of mast cells in the PCa tissue was assessed by the histochemical method. Results. The analysis of the expression levels of tumor-associated miRNAs demonstrated that the tumor tissue of patients with a high risk of PCa progression was characterized by 4.93 (p < 0.01) and 8.97 (p < 0.05) times higher levels of miR-19a-3p and miR-23b-3p, respectively, compared to similar indicators in the group of patients with a low risk of PCa progression. The levels of miR-7-5p and miR-19a-3p expression in the PCa tissue correlated with the expression level of α-SMA (r = 0.49 and r = 0.45, respectively; p < 0.05) and VIM (r = 0.45 and r = 0.46; respectively, p < 0.05). A direct relationship (r = 0.44; p < 0.05) was established between the level of miR-7-5p expression and the degree of infiltration of the prostate gland tissue by tumor-associated macrophages. Conclusions. The features of the expression of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p indicated the prospect of their use as markers of the aggressiveness of the PCa course.
... The homing behavior of NK cells is mainly dependent on the signal transduction between the homing receptor on the surface and the ligand, while the infiltration of NK cells is influenced by the interaction with TME [106,107]. Studies have found that once NK cells infiltrate tumor cells and homing receptors bind to ligands, immune cell activation signals will be transmitted and secrete perforin, granzyme and apoptosis-inducing factors [108] to play an anti-tumor immune role of NK cells. Therefore, it is necessary to use nanomaterials to enhance the homing and infiltration of NK cells to inhibit tumor development. ...
Tumor immunotherapy represented by immune target blocking and chimeric antigen receptor cell therapy has developed rapidly. Among them, Natural Killer Cell (NK) is gradually becoming another preferred immunotherapy method after T cell immunotherapy because of its unique killing effect in innate immunity and adaptive immunity. Although NK cell therapy has achieved promising results in clinical trials, there are still some problems, such as low efficacy in solid tumors, insufficient penetration of NK cells and high cost of treatment. Nanomaterials are expected to be an excellent tool to improve the anti-tumor immune response of NK cells due to their advantages such as chemical specificity, biocompatibility and simple synthesis. Nanomaterials can enhance the cytotoxicity of NK cells, participate in the modification and noninvasive cell-tracking patterns of NK cells，and mediate their homing and infiltration, and thus significantly improve the efficiency of NK cell immunotherapy. In this review, we will briefly introduce the methods and mechanisms of tumor immunotherapy, emphasize the research progress of NK cell-based immunotherapy and imaging, and finally summarize the direction and research progress of nanomaterials in NK cell-based immunotherapy.
... Because immune cell infiltration affects cancer progression [20][21][22], immune cells have been proposed as possible delivery vehicles for gene therapy [23]. HSCs can infiltrate tumors to fight disease progression, but exhibit only limited infiltration in lung tumors [24]. ...
Lung cancer makes up one-fourth of all cancer-related mortality with the highest mortality rate among all cancers. Despite recent scientific advancements in cancer therapeutics, the 5-year survival rate of lung adenocarcinoma (LUAD) cancer patients remains below 15 percent. It has been suggested that the high mortality rate of LUAD is linked to the acquisition of progenitor-like cells with stem-like characteristics that assist the whole tumor in regulating immune cell infiltration. To examine this hypothesis further, this study mined several databases to explore the presence of stemness-related genes and miRNAs in LUAD cancers. We examine their association with immune and accessory cell infiltration rates and patient survival. We found 3 stem cell-related genes, ORC1L, KIF20A, and DLGAP5, present in LUAD that also correlate with changes in immune infiltration rates and reduced patient survival rates. Additionally, the modulation in myeloid-derived suppressor cell (MDSC) infiltration and miRNA hsa-mir-1247-3p mediated targeting of tumor suppressor SLC24A4 and oncogenes RAB3B and HJURP appears to primarily regulate LUAD patient survival. Given these findings, hsa-mir-1247-3p and/or its associated gene targets may offer a promising avenue to enhance patient survivability.
... A number of segmentation models based on convolutional neural networks (CNNs) have also been extensively researched. However, noise, stumpy contrast, unclear boundaries, various tumour sizes, and forms make it difficult to precisely split breast tumor cells on ultrasound pictures [10]. Additionally, the majority of traditional techniques only trained one network for tumour pixel segmentation [11]. ...
... There are 780 pictures here, and on average, each one is 500 pixels wide and tall. Normal (133 shots), malignant (210 images), and benign (487 images) are the three primary groups represented in this collection, as shown in Figure 1 [10]. This whole dataset was divided into training and testing set with a 50/50 split. ...
... The breast ultrasound (BUS) images utilized in this research are from open-source databases [10]. Seven hundred eighty ultrasound scans from women aged 25 to 75 made up the BUSI dataset. ...
Breast cancer diagnosis relies on breast ultra-sound (BUS) and the early breast cancer screening saves lives. Computer-aided design (CAD) tools diagnose tumours via BUS tumour segmentation. Thus, breast cancer analysis automation may aid radiologists. Early detection of breast cancer might help the patients to survive and in context with this many approaches have been demonstrated by different researches, however, some of the works are weak in the segmentation of breast cancer images. to tackle these issues, this study propose a novel Hybrid Attendseg based gravitational clustering optimization (HA-GC) method which is utilized to segment breast cancer as normal malignant , and benign. For this we have taken the dataset known as breast ultrasound (BUS) images. This method constructively segments the breast cancer images. Prior to the segmen-tation, pre-processing is carried out which can be used to normalize the images incorporated with the removal of unwanted noises and format the images Optimization selects the best qualities. An experiment is conducted and compared the results with the parameters such as Dice coefficient, Jacquard, Precision, and Recall and attained over 90% and ensures the usage of present work in the segmentation of breast cancer images.
... Tumor-infiltrating immune cells (TIICs) have been used for the prediction of prognosis and treatment in cancer patients and they are crucial components of tumor microenvironments [4]. Tumor-infiltrating lymphocytes (TILs), first described by Clark et al. [5], are T cells, B cells, and natural killer cells that are the most widely studied populations of TIICs and their correlation with favorable outcomes in HCC has been reported previously [6]. ...
Purpose
Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers. However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role.
Methods
Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis.
Results
The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049).
Conclusion
This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.
