The gut microbiome plays an important role in systemic inflammation and immune response. Microbes can translocate and reside in tumour niches. However, it is unclear how the intratumour microbiome ...affects immunity in human cancer. The purpose of this study was to investigate the association between intratumour bacteria, infiltrating CD8+ T cells and patient survival in cutaneous melanoma.
Using The Cancer Genome Altas's cutaneous melanoma RNA sequencing data, levels of intratumour bacteria and infiltrating CD8+ T cells were determined. Correlation between intratumour bacteria and infiltrating CD8+ T cells or chemokine gene expression and survival analysis of infiltrating CD8+ T cells and Lachnoclostridium in cutaneous melanoma were performed.
Patients with low levels of CD8+ T cells have significantly shorter survival than those with high levels. The adjusted hazard ratio was 1.57 (low vs high) (95% confidence interval: 1.17–2.10, p = 0.002). Intratumour bacteria of the Lachnoclostridium genus ranked top in a positive association with infiltrating CD8+ T cells (correlation coefficient = 0.38, p = 9.4 × 10−14), followed by Gelidibacter (0.31, p = 1.13 × 10−9), Flammeovirga (0.29, p = 1.96 × 10−8) and Acinetobacter (0.28, p = 8.94 × 10−8). These intratumour genera positively correlated with chemokine CXCL9, CXCL10 and CCL5 expression. The high Lachnoclostridium load significantly reduced the mortality risk (p = 0.0003). However, no statistically significant correlation was observed between intratumour Lachnoclostridium abundance and the levels of either NK, B or CD4+ T cells.
Intratumour-residing gut microbiota could modulate chemokine levels and affect CD8+ T-cell infiltration, consequently influencing patient survival in cutaneous melanoma. Manipulating the intratumour gut microbiome may benefit patient outcomes for those undergoing immunotherapy.
•High infiltration of cytotoxic CD8+ T cells benefits outcomes of patients with melanoma.•Intratumour bacteria are associated with the infiltration of cytotoxic CD8+ T cells.•Intratumour bacteria might affect the chemokines for migration of CD8+ T cells.•The high Lachnoclostridium load in tumour significantly reduced the mortality risk.
Titanium dioxide (TiO2) nanoparticles were decorated with different amounts of silver nanoparticles (AgNPs) using an electrochemically active biofilm (EAB), which is a biogenic approach that leads to ...the formation of Ag@TiO2 nanocomposites. UV-vis spectroscopy, photoluminescence, X-ray diffraction and electron microscopy showed AgNPs, 2-5 nm in size, well-dispersed and anchored to the TiO2 surface and overall synthesis of Ag@TiO2 nanocomposites. The photocatalytic performance of the as-synthesized Ag@TiO2 nanocomposites was evaluated in terms of their efficiency for the photodecomposition of methylene blue (MB) in an aqueous solution under visible light irradiation. The nanocomposites showed exceptionally high photodecomposition efficiency (>7 times) compared to commercial TiO2 (Sigma). The enhanced photocatalytic activity was attributed to the synergistic contribution of both a delayed charge recombination rate caused by the high electronic mobility of the AgNPs and the increased surface area originating from the nanometer sized AgNPs on TiO2. The nanocomposites also showed exceptionally high stability and reusability under similar experimental conditions.
The emergence of cloud infrastructure has the potential to provide significant benefits in a variety of areas in the medical imaging field. The driving force behind the extensive use of cloud ...infrastructure for medical image processing is the exponential increase in the size of computed tomography (CT) and magnetic resonance imaging (MRI) data. The size of a single CT/MRI image has increased manifold since the inception of these imagery techniques. This demand for the introduction of effective and efficient frameworks for extracting relevant and most suitable information (features) from these sizeable images. As early detection of lungs cancer can significantly increase the chances of survival of a lung scanner patient, an effective and efficient nodule detection system can play a vital role. In this article, we have proposed a novel classification framework for lungs nodule classification with less false positive rates (FPRs), high accuracy, sensitivity rate, less computationally expensive and uses a small set of features while preserving edge and texture information. The proposed framework comprises multiple phases that include image contrast enhancement, segmentation, feature extraction, followed by an employment of these features for training and testing of a selected classifier. Image preprocessing and feature selection being the primary steps—playing their vital role in achieving improved classification accuracy. We have empirically tested the efficacy of our technique by utilizing the well‐known Lungs Image Consortium Database dataset. The results prove that the technique is highly effective for reducing FPRs with an impressive sensitivity rate of 97.45%.
A novel classification framework for lungs nodule classification is proposed to reduce false positive rate and achieve impressive sensitivity rate. It is computationally effective, precise results by using few features while preserving edge and texture information.
Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤ 5 cumulative metastasis(es), termed oligometastases. In contrast ...to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.
Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.
Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.
These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ten-Eleven-Translocation-2 (Tet2) is a DNA methylcytosine dioxygenase that functions as a tumor suppressor in hematopoietic malignancies. We examined the role of Tet2 in tumor-tissue myeloid cells ...and found that Tet2 sustains the immunosuppressive function of these cells. We found that Tet2 expression is increased in intratumoral myeloid cells both in mouse models of melanoma and in melanoma patients and that this increased expression is dependent on an IL-1R-MyD88 pathway. Ablation of Tet2 in myeloid cells suppressed melanoma growth in vivo and shifted the immunosuppressive gene expression program in tumor-associated macrophages to a proinflammatory one, with a concomitant reduction of the immunosuppressive function. This resulted in increased numbers of effector T cells in the tumor, and T cell depletion abolished the reduced tumor growth observed upon myeloid-specific deletion of Tet2. Our findings reveal a non-cell-intrinsic, tumor-promoting function for Tet2 and suggest that Tet2 may present a therapeutic target for the treatment of non-hematologic malignancies.
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•Deletion of Tet2 in myeloid cells reduces melanoma tumor burden•Tet2 expression is induced via the IL-1R-MyD88 axis in tumor-associated macrophages•Tet2 maintains myeloid immunosuppressive function and the associated genetic program•Myeloid-specific Tet2 deletion results in higher numbers of tumor-infiltrating T cells
The DNA methylcytosine dioxygenase Tet2 functions as a tumor suppressor in multiple contexts, including hematopoietic malignancies. Pan et al. now reveal a tumor-promoting role for Tet2, whereby Tet2 functions to sustain an immunosuppressive program in myeloid cells that in turn dampens the anti-tumor T cell response.
Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by ...limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy.
We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent.
Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset.
Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Somatic mutation-derived neoantigens are associated with patient survival in breast and ovarian cancer. These neoantigens are targets for cancer, as shown by the implementation of neoepitope peptides ...as cancer vaccines. The success of cost-effective multi-epitope mRNA vaccines against SARS-Cov-2 in the pandemic established a model for reverse vaccinology. In this study, we aimed to develop an in silico pipeline designing an mRNA vaccine of the CA-125 neoantigen against breast and ovarian cancer, respectively. Using immuno-bioinformatics tools, we predicted cytotoxic CD8+ T cell epitopes based on somatic mutation-driven neoantigens of CA-125 in breast or ovarian cancer, constructed a self-adjuvant mRNA vaccine with CD40L and MHC-I -targeting domain to enhance cross-presentation of neoepitopes by dendritic cells. With an in silico ImmSim algorithm, we estimated the immune responses post-immunization, showing IFN-γ and CD8+ T cell response. The strategy described in this study may be scaled up and implemented to design precision multi-epitope mRNA vaccines by targeting multiple neoantigens.
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