T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.

The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear.

Effect of immune checkpoint inhibitor time-of-day infusion on survival in advanced biliary tract cancer: a propensity score-matched analysis.

Background: Circadian rhythms in the immune system and anti-tumor responses are underexplored in cancer immunotherapy. Despite the success of immune checkpoint inhibitors (ICIs) in treating advanced biliary tract cancers (BTCs), not all patients benefit. This study examined whether the timing of ICI administration affects outcomes in advanced BTC patients.

Prognostic Significance of CCDC8 in Bladder Cancer: Insights from Bioinformatics and Immunohistochemical Analysis.

Pro-apoptotic coiled-coil domain containing 8 (CCDC8) has been linked to tumor progression and metastasis, yet its prognostic significance and underlying molecular mechanisms in bladder cancer remain to be elucidated. This study utilized raw data from public databases along with a single-center retrospective case series. We performed bioinformatics analysis and immunohistochemistry to investigate the biological landscape of CCDC8 in various tumors, with a particular focus on bladder cancer.

Quantitative Histopathology Analysis Based on Label-free Multiphoton Imaging for Breast Cancer Diagnosis and Neoadjuvant Immunotherapy Response Assessment.

Accurate diagnosis and assessment of breast cancer treatment responses are critical challenges in clinical practice, influencing patient treatment strategies and ultimately long-term prognosis. Currently, diagnosing breast cancer and evaluating the efficacy of neoadjuvant immunotherapy (NAIT) primarily rely on pathological identification of tumor cell morphology, count, and arrangement. However, when tumors are small, the tumors and tumor beds are difficult to detect; relying solely on tumor cell identification may lead to false negatives.

Bone marrow niches orchestrate stem-cell hierarchy and immune tolerance.

Stem cells reside in specialized microenvironments, termed niches, at several different locations in tissues. The differential functions of heterogeneous stem cells and niches are important given the increasing clinical applications of stem-cell transplantation and immunotherapy. Whether hierarchical structures among stem cells at distinct niches exist and further control aspects of immune tolerance is unknown.

Specifically blocking αvβ8-mediated TGF-β signaling to reverse immunosuppression by modulating macrophage polarization.

Background: Targeting the TGF-β pathway in tumor therapy has proven challenging due to the highly context-dependent functions of TGF-β. Integrin αvβ8, a pivotal activator of TGF-β, has been implicated in TGF-β signaling within tumors, as demonstrated by the significant anti-tumor effects of anti-αvβ8 antibodies. Nevertheless, the expression profile of αvβ8 remains a subject of debate, and the precise mechanisms underlying the anti-tumor effects of anti-αvβ8 antibodies are not yet fully elucidated.

Targeted Treatment of Metastatic Triple-Negative Breast Cancer: A Systematic Review.

Introduction: Triple-negative breast cancer (TNBC) is a subgroup of breast cancer characterized by the absence of estrogen and the human epidermal 2 receptor and also a lack of targeted therapy options. Chemotherapy has so far been the only approved treatment option, and patients with metastatic cancer have a dismal prognosis with a median overall survival (OS) of approximately 14 months. Identification of druggable targets for metastatic TNBC is therefore of special interest.

CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases?

Autoimmune rheumatic diseases (ARDs), such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, involve dysregulated immune responses causing chronic inflammation and tissue damage. Despite advancements in clinical management, many patients do not respond to current treatments, which often show limited efficacy due to the persistence of autoreactive B cells. Chimeric antigen receptor (CAR)-T cell therapy, which has shown success in oncology for B cell malignancies, targets specific antigens and involves the adoptive transfer of genetically engineered T cells.

Up-regulation of Cuproptosis-related lncRNAS in Patients Receiving Immunotherapy for Metastatic Clear Cell Renal Cell Carcinoma Indicates Progressive Disease.

Background/aim: Clear cell renal cell carcinoma (ccRCC) represents the most common type of renal cancer. When resectable, nephrectomy is the only radical treatment for ccRCC, however metastasis is already present at 30% of the patient population. Although great progress has been made in the field of targeted therapy with the emergence of immune checkpoint inhibitors (ICIs) the cure of metastatic ccRCC (mccRCC) remains far from achieved.

A Narrative Review of the Role of Immunotherapy in Metastatic Carcinoma of the Colon Harboring a BRAF Mutation.

Patients affected by metastatic carcinoma of the colon/rectum (mCRC) harboring mutations in the BRAF gene (MBRAF) respond poorly to conventional therapy and have a prognosis worse than that of patients without mutations. Despite the promising outcomes of targeted therapy utilizing multi-targeted inhibition of the mitogen-activated protein kinase (MAPK) signaling system, the therapeutic efficacy, especially for the microsatellite stable/DNA proficient mismatch repair (MSS/PMMR) subtype, remains inadequate. Patients with MBRAF/mCRC and high microsatellite instability or DNA deficient mismatch repair (MSI-H/DMMR) exhibit a substantial tumor mutation burden, suggesting a high probability of response to immunotherapy.

Decoding KRAS mutation in non-small cell lung cancer patients receiving immunotherapy: A retrospective institutional comparison and literature review.

Introduction: KRAS mutation the most common molecular alteration in advanced non-small cell lung cancer (NSCLC) and is associated with an unfavourable prognosis, largely due to the lack of targeted therapeutic options for the majority of the KRAS mutated isoforms. The landscape of NSCLC treatment has expanded with the introduction of immune checkpoint inhibitors (ICIs). Nonetheless, data regarding the efficacy of ICI in NSCLC patients harbouring KRAS mutations are conflicting.

Enrichment of Cancer-Associated Fibroblasts, Macrophages, and Up-Regulated TNF-α Signaling in the Tumor Microenvironment of CMS4 Colorectal Peritoneal Metastasis.

Background: Metastatic colorectal cancer (mCRC) is the main cause of CRC mortality, with limited treatment options. Although immunotherapy has benefited some cancer patients, mCRC typically lacks the molecular features that respond to this treatment. However, recent studies indicate that the immune microenvironment of mCRC may be modified to enhance the effect of immune checkpoint inhibitors.

Intratumoural CD8 CXCR5 follicular cytotoxic T cells have prognostic value and are associated with CD19 CD38 B cells and tertiary lymphoid structures in colorectal cancer.

Background: Colorectal cancer (CRC) is the most common digestive cancer in the world. Microsatellite stability (MSS) and microsatellite instability (MSI-high) are important molecular subtypes of CRC closely related to tumor occurrence and progression and immunotherapy efficacy. The presence of CD8 CXCR5 follicular cytotoxic T (T) cells is strongly associated with autoimmune disease and CD8 effector function.

Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.

Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.

Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset.

Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma.

Background: Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenvironment are not fully understood. This study investigated the impact of HNF1B on colon cancer immunotherapy in depth.

Towards designing improved cancer immunotherapy targets with a peptide-MHC-I presentation model, HLApollo.

Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins.

Precise identification of somatic and germline variants in the absence of matched normal samples.

Somatic variants play a crucial role in the occurrence and progression of cancer. However, in the absence of matched normal controls, distinguishing between germline and somatic variants becomes challenging in tumor samples. The existing tumor-only genomic analysis methods either suffer from limited performance or insufficient interpretability due to an excess of features.

Reduced irradiation exposure areas enhanced anti-tumor effect by inducing DNA damage and preserving lymphocytes.

Background: Partial stereotactic body radiation therapy (SBRT) targeting hypoxic regions of large tumors (SBRT-PATHY) has been shown to enhance the efficacy of tumor radiotherapy by harnessing the radiation-induced immune response. This approach suggests that reducing the irradiation target volume not only achieves effective anti-tumor effects but also minimizes damage to surrounding normal tissues. In this study, we evaluated the antitumor efficacy of reduced-tumour-area radiotherapy (RTRT) , and explored the relationship between tumor control and immune preservation and the molecular mechanisms underlying of them.

Prognostic Value of / Status for Overall Survival in First-Line Monoimmunotherapy and Chemoimmunotherapy Treated Patients With Nonsquamous NSCLC in the Netherlands: A Brief Report.

Introduction: Programmed death-ligand 1 (PD-L1) is the main predictive biomarker used to identify patients with NSCLC who are eligible for treatment with immune checkpoint inhibitors. Despite its utility, the predictive capacity of PD-L1 is limited, necessitating the exploration of supplementary predictive biomarkers. In this report, we describe the prognostic value of / mutation status for overall survival (OS) in patients with NSCLC treated with first-line immunotherapy or combined chemoimmunotherapy.

Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths with a 5-year survival rate of 13%. Surgical resection remains the only curative option as systemic therapies offer limited benefit. Poor response to chemotherapy and immunotherapy is due, in part, to the dense stroma and heterogeneous tumor microenvironment (TME).

Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3.

Background: Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.

Methods: We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases.

Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer: a phase II trial of pembrolizumab.

Background: Immune checkpoint inhibitors (ICIs) are effective in a subset of patients with metastatic solid tumors. However, the patients who would benefit most from ICIs in biliary tract cancer (BTC) are still controversial.

Materials And Methods: We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line therapy.

Multi-omics analysis-based clinical and functional significance of a novel prognostic and immunotherapeutic gene signature derived from amino acid metabolism pathways in lung adenocarcinoma.

Background: Studies have shown that tumor cell amino acid metabolism is closely associated with lung adenocarcinoma (LUAD) development and progression. However, the comprehensive multi-omics features and clinical impact of the expression of genes associated with amino acid metabolism in the LUAD tumor microenvironment (TME) are yet to be fully understood.

Methods: LUAD patients from The Cancer Genome Atlas (TCGA) database were enrolled in the training cohort.