Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma.

Background: Cancer immune evasion is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Current immunotherapies combat this issue by reinstating immunosurveillance of tumors; however, it benefits a limited patient population. Thus, a more effective immunotherapeutic strategy is warranted to cater to specific patient populations.

Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8--methylfusarubin for breast cancer treatment.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8--methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand.

Hippo pathway in cancer cells induces NCAM1αSMA fibroblasts to modulate tumor microenvironment.

Cancer cells adeptly manipulate the tumor microenvironment (TME) to evade host antitumor immunity. However, the role of cancer cell-intrinsic signaling in shaping the immunosuppressive TME remains unclear. Here, we found that the Hippo pathway in cancer cells orchestrates the TME by influencing the composition of cancer-associated fibroblasts (CAFs).

Mesothelin- and nucleolin-specific T cells from combined short peptides effectively kill triple-negative breast cancer cells.

Background: Triple-negative breast cancer (TNBC), known for its aggressiveness and limited treatment options, presents a significant challenge. Adoptive cell transfer, involving the ex vivo generation of antigen-specific T cells from peripheral blood mononuclear cells (PBMCs), emerges as a promising approach. The overexpression of mesothelin (MSLN) and nucleolin (NCL) in TNBC samples underscores their potential as targets for T cell therapy.

advancements in Peptide-MHC interaction: A molecular dynamics study of predicted glypican-3 peptides and HLA-A*11:01.

Our study employed molecular dynamics (MD) simulations to assess the binding affinity between short peptides derived from the tumor-associated antigen glypican 3 (GPC3) and the major histocompatibility complex (MHC) molecule HLA-A*11:01 in hepatocellular carcinoma. We aimed to improve the reliability of predictions of peptide-MHC interactions, which are crucial for developing targeted cancer therapies. We used five algorithms to discover four peptides (TTDHLKFSK, VINTTDHLK, KLIMTQVSK, and STIHDSIQY), demonstrating the substantial potential for HLA-A11:01 presentation.

Identification of Tumor Budding-Associated Genes in Breast Cancer through Transcriptomic Profiling and Network Diffusion Analysis.

Breast cancer has the highest diagnosis rate among all cancers. Tumor budding (TB) is recognized as a recent prognostic marker. Identifying genes specific to high-TB samples is crucial for hindering tumor progression and metastasis.

PseudoCell: Hard Negative Mining as Pseudo Labeling for Deep Learning-Based Centroblast Cell Detection.

Deep learning models for patch classification in whole-slide images (WSIs) have shown promise in assisting follicular lymphoma grading. However, these models often require pathologists to identify centroblasts and manually provide refined labels for model optimization. To address this limitation, we propose , an object detection framework for automated centroblast detection in WSI, eliminating the need for extensive pathologist's refined labels.

The combined tumour-based Fascin/Snail and stromal periostin reveals the effective prognosis prediction in colorectal cancer patients.

Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients' prognosis were invesigated.

Histopathological tumour microenvironment score independently predicts outcome in primary operable colorectal cancer.

Colorectal cancer (CRC) is a heterogenous malignancy and research is focused on identifying novel ways to subtype patients. In this study, a novel classification system, tumour microenvironment score (TMS), was devised based on Klintrup-Mäkinen grade (KMG), tumour stroma percentage (TSP), and tumour budding. TMS was performed using a haematoxylin and eosin (H&E)-stained section from retrospective CRC discovery and validation cohorts (n = 1,030, n = 787).

BRCA1 deficiency enhances the aggressiveness of breast cancer cells expressing HPV16 oncoproteins.

Background Information: The precise etiology of breast cancer is not completely understood, although women with BRCA1 gene mutations have a significantly increased risk of developing the disease. In addition, sporadic breast cancer is frequently associated with decreased BRCA1 gene expression. Growing evidence of Human papillomaviruses (HPVs) infections in breast tumors has raised the possibility of the involvement of HPVs in the pathogenesis of breast cancer.

Targeting MYC at the intersection between cancer metabolism and oncoimmunology.

MYC activation is a known hallmark of cancer as it governs the gene targets involved in various facets of cancer progression. Of interest, MYC governs oncometabolism through the interactions with its partners and cofactors, as well as cancer immunity via its gene targets. Recent investigations have taken interest in characterizing these interactions through multi-Omic approaches, to better understand the vastness of the MYC network.

Detection of centroblast cells in H&E stained whole slide image based on object detection.

Introduction: Detection and counting of Centroblast cells (CB) in hematoxylin & eosin (H&E) stained whole slide image (WSI) is an important workflow in grading Lymphoma. Each high power field (HPF) patch of a WSI is inspected for the number of CB cells and compared with the World Health Organization (WHO) guideline that organizes lymphoma into 3 grades. Spotting and counting CBs is time-consuming and labor intensive.

Stimulating T cell responses against patient-derived breast cancer cells with neoantigen peptide-loaded peripheral blood mononuclear cells.

Breast cancer stands as a formidable global health challenge for women. While neoantigens exhibit efficacy in activating T cells specific to cancer and instigating anti-tumor immune responses, the accuracy of neoantigen prediction remains suboptimal. In this study, we identified neoantigens from the patient-derived breast cancer cells, PC-B-142CA and PC-B-148CA cells, utilizing whole-genome and RNA sequencing.

Anti-PD-L1 × anti-CD3 bispecific T-cell engager-armed T cells can overcome immunosuppression and redirect T cells to kill breast cancer cells expressing PD-L1.

T cell-based immunotherapy has transformed cancer treatment. Nonetheless, T cell antitumor activity can be inhibited by an immune checkpoint molecule expressed on cancer cells, program death ligand 1 (PD-L1), which interacts with the PD-1 on T cells. We generated αPD-L1 × αCD3 bispecific T-cell engager-armed T cells (BATs) to prevent PD-L1/PD-1 interaction and hence to redirect T cells to kill cancer cells.

Enhancement of PD-L1-attenuated CAR-T cell function through breast cancer-associated fibroblasts-derived IL-6 signaling via STAT3/AKT pathways.

Background: Carcinoma-associated fibroblasts (CAFs) play a critical role in cancer progression and immune cell modulation. In this study, it was aimed to evaluate the roles of CAFs-derived IL-6 in doxorubicin (Dox) resistance and PD-L1-mediated chimeric antigenic receptor (CAR)-T cell resistance in breast cancer (BCA).

Methods: CAF conditioned-media (CM) were collected, and the IL-6 level was measured by ELISA.

Nucleolin‑based targeting strategies in cancer treatment: Focus on cancer immunotherapy (Review).

The benefits of treating several types of cancers using immunotherapy have recently been established. The overexpression of nucleolin (NCL) in a number of types of cancer provides an attractive antigen target for the development of novel anticancer immunotherapeutic treatments. NCL is a multifunctional protein abundantly distributed in the nucleus, cytoplasm and cell membrane.

Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer.

Purpose: Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Despite a well-established knowledge of tumour development, biomarkers to predict patient outcomes are still required. S100 calcium-binding protein A2 (S100A2) has been purposed as a potential marker in many types of cancer, however, the prognostic value of S100A2 in CRC is rarely reported.

β-Catenin Drives Butyrophilin-like Molecule Loss and γδ T-cell Exclusion in Colon Cancer.

Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs.

Carbonic anhydrase IX-related tumoral hypoxia predicts worse prognosis in breast cancer: A systematic review and meta-analysis.

Background: Tumoral hypoxia is associated with aggressiveness in many cancers including breast cancer. However, measuring hypoxia is complicated. Carbonic anhydrase IX (CAIX) is a reliable endogenous marker of hypoxia under the control of the master regulator hypoxia-inducible factor-1α (HIF-1α).

Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis.

Tenosynovial giant cell tumor (TGCT) is a mesenchymal tumor derived from the synovium of the tendon sheath and joints, most frequently in the large joints. The standard of care for TGCTs is surgical resection. A new targeting approach for treating TGCTs has emerged from studies on the role of the CSF1/CSF1 receptor (CSF1R) in controlling cell survival and proliferation during the pathogenesis of TGCTs.

Cellular localization of nucleolin determines the prognosis in cancers: a meta-analysis.

Nucleolin (NCL) is a multifunctional protein expressed in the nucleus, cytoplasm, and cell membrane. Overexpression of NCL has a controversial role as a poor prognostic marker in cancers. In this study, a meta-analysis was performed to evaluate the prognostic value of NCL in different subcellular localizations (cytoplasmic (CyNCL) and nuclear (NuNCL)) across a range of cancers.

Activation of cytotoxic T lymphocytes by self-differentiated myeloid-derived dendritic cells for killing breast cancer cells expressing folate receptor alpha protein.

Adoptive cell transfer (ACT) is a promising approach for cancer treatment. Activation of T lymphocytes by elf-differentiated yeloid-derived ntigen-presenting-cells eactive against umor (SmartDC) resulted in specific anti-cancer function. Folate receptor alpha (FRα) is highly expressed in breast cancer (BC) cells and thus potential to be a target antigen for ACT.

The relationship between the Glasgow Microenvironment Score and markers of epithelial-mesenchymal transition in TNM II-III colorectal cancer.

Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) markers in CRC have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC.

Mesothelin‑specific T cell cytotoxicity against triple negative breast cancer is enhanced by 40s ribosomal protein subunit 3‑treated self‑differentiated dendritic cells.

Triple negative breast cancer (TNBC) lacks targeted treatment resulting in poor prognosis. Targeting overexpressing mesothelin (MSLN) using MSLN‑specific T cells is an attractive treatment approach and the aim of the present study. The expression of MSLN in human TNBC paraffin sections was analyzed by immunohistochemistry.