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2026 Update on the Management of Diffuse Large B-Cell Lymphoma - PubMed
3 months ago
- Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in the Western Hemisphere.
- R-CHP remains the backbone of therapy, with frontline options including pola-R-CHP and R-CHOP for fit patients, and R-mini-CHOP or palliation for elderly/frail patients.
- Frontline trials focus on improving outcomes for high-risk patients using R-CHOP combined with novel agents, CAR-T, and bispecific antibodies.
- Risk-adapted approaches targeting cell of origin (COO) and utilizing interim PET imaging or ctDNA are under investigation.
- Second-line curative-intent therapies include CAR-T or autologous stem cell transplantation, depending on disease progression timing.
- Relapsed/refractory DLBCL treatments have expanded, including bispecific antibody combinations, antibody-drug conjugates, and targeted therapies.
- Ongoing trials aim to reduce chemotherapy reliance, exploring targeted therapy-antibody combinations, immunomodulatory agents, and cellular therapies.
Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment - PubMed
3 months ago
- Sensory neurons play a critical role in the immune-excluded tumor microenvironment (TME) of triple-negative breast cancer (TNBC).
- Nerve growth factor (NGF) in TME triggers sensory neurons to secrete calcitonin gene-related peptide (CGRP).
- CGRP activates cancer-associated fibroblasts (CAFs) via RAMP1 receptor, increasing collagen deposition through cAMP/PKA/CREB1 signaling.
- Targeting sensory neurons remodels TME and enhances anti-PD-1 immunotherapy efficacy in TNBC.
- CGRP antagonist rimegepant shows potential as an immuno-sensitizer to improve immunotherapy outcomes.
Atlas-guided discovery of transcription factors for T cell programming - PubMed
3 months ago
- CD8+ T cells differentiate into diverse states impacting immune responses in cancer and chronic infection.
- A comprehensive atlas integrating transcriptional and epigenetic data across nine CD8+ T cell states was built to infer TF activity profiles.
- The study focused on two critical T cell states: terminally exhausted T (TEXterm) cells and tissue-resident memory T (TRM) cells.
- Global TF community analysis revealed distinct pathways and networks underlying protective (TRM) versus dysfunctional (TEXterm) states.
- In vivo CRISPR screening with single-cell RNA sequencing identified TFs governing TEXterm cell differentiation.
- HIC1 and GFI1 were identified as shared regulators of TEXterm and TRM cell differentiation, while KLF6 uniquely regulates TRM cells.
- New TEXterm-selective TFs, ZSCAN20 and JDP2, were discovered with no prior known function in T cells.
- Targeted deletion of ZSCAN20 and JDP2 enhanced tumor control and synergized with immune checkpoint blockade without affecting TRM cell formation.
- Depletion of these TFs in human T cells reduced inhibitory receptor expression and improved effector function.
- The platform enables precise engineering of T cell states for more effective cellular immunotherapies.
Noninvasive imaging-based assessment of tumor-associated neutrophils for prognosis and immunotherapy response in gastric cancer: a multicenter study - PubMed
3 months ago
- Noninvasive CT-based ensemble machine learning radiomic biomarker (EnmlbaRB) developed for mapping tumor-associated neutrophils (TAN) infiltration in gastric cancer.
- Multicenter study involving 2,170 gastric cancer patients across eight cohorts, validated in six independent cohorts including 177 anti-PD-1-treated patients.
- EnmlbaRB predicted TAN status with an AUC of 0.71 and 80.74% specificity, showing robust performance.
- TAN-Low patients had significantly superior 5-year overall survival compared to TAN-High patients (e.g., 64.12% vs. 46.78%, p < 0.05).
- In anti-PD-1 cohorts, TAN-Low subgroups showed 1.9-fold higher disease control rates (83.9% vs 44.1%; p < 0.001) and prolonged median progression-free survival (>41.9 vs 6.2 months; HR = 0.162, p < 0.001).
- First clinically validated noninvasive solution for TAN infiltration mapping in gastric cancer, aiding in prognosis and immunotherapy response prediction.
ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment - PubMed
3 months ago
- ITGB1 plays a critical role in triple-negative breast cancer (TNBC) development by modulating the tumor microenvironment (TME).
- In vivo CRISPR screens identified ITGB1 as a key regulator, influencing tumor-associated myeloid populations and immune cell infiltration.
- Suppression of ITGB1 promotes anti-tumorigenic myeloid cells and enhances CD4 and CD8 T cell infiltration, improving antitumor effects.
- A novel functional domain in ITGB1, distinct from known ligand-binding sites, was discovered to be essential for its pro-tumorigenic activity.
- An antibody targeting this domain significantly impaired TNBC progression, suggesting ITGB1 as a promising therapeutic target.
- The study provides insights into TNBC development mechanisms and proposes a unique strategy for ITGB1-targeted therapy.
Randomized Trial Links Time of Day to Immunotherapy Success - PubMed
3 months ago
- Morning administration of checkpoint inhibitors significantly extended survival in patients with advanced non-small cell lung cancer.
- First randomized trial of immunotherapy timing links time of day to treatment success.
- Results support aligning treatment with circadian biology to improve cancer outcomes.
Oncolytic virus OH2 induces PD-L1 upregulation via NF-κB signaling and synergizes with anti-PD-L1 therapy in prostate cancer through a targeted extracellular vesicle delivery system - PubMed
3 months ago
- Oncolytic virus OH2 shows efficacy in killing prostate cancer cells but upregulates PD-L1 via NF-κB signaling, leading to adaptive immune resistance.
- A novel targeted delivery system, OH2@RRA-AP-EVs, was developed to enhance tumor targeting and enable ROS-triggered PD-L1 blockade.
- Intravenous administration of OH2@RRA-AP-EVs resulted in 70% greater tumor growth inhibition compared to free OH2 and enhanced CD8+ T cell infiltration.
- The study provides a mechanism for OH2-induced PD-L1 expression and introduces a versatile delivery platform for viro-immunotherapy in prostate cancer.
Kitasamycin overcomes ferroptosis and immunotherapy resistance by targeting the HUWE1-NCOA4-FTH1 Axis - PubMed
3 months ago
- Kitasamycin, a macrolide antibiotic, was identified as a potent ferroptosis sensitizer in vitro and in vivo.
- Kitasamycin competitively binds to HUWE1, inhibiting its E3 ubiquitin ligase activity, stabilizing NCOA4, and activating the NCOA4-FTH1 ferritinophagy axis.
- The study found that kitasamycin induces immunogenic ferroptosis and reshapes anti-tumor T-cell immunity.
- Kitasamycin enhances immune checkpoint blockade (ICB) efficacy and overcomes ICB resistance in multiple preclinical melanoma models.
- A high NCOA4 and low HUWE1 signature correlates with ferroptosis activation, increased T-cell infiltration, and improved survival in ICB-treated patients.
- The findings suggest kitasamycin as a promising adjunct to immunotherapy for cancer patients needing concurrent antibiotic therapy.
Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy - PubMed
3 months ago
- Vascular smooth muscle cell (VSMC) diversification is a key driver of atherosclerotic coronary artery disease (CAD).
- Fibroblast activation protein (FAP) was identified as a marker of modulated VSMCs through multiomic single-cell profiling and spatial transcriptomics.
- Lineage tracing in mice showed that FAP+ cells originate from Myh11+ VSMCs, and FAP PET imaging in CAD patients confirmed plaque uptake.
- FAP+ cell states were found in the macrophage-rich neo-intima.
- An anti-FAP bispecific T-cell engager was developed, reducing plaque burden and remodeling the stromal-immune microenvironment via T-cell clonal expansion.
- The study provides a single-cell and spatial atlas of human CAD and highlights immunotherapy for lipid-independent targets.
Deficiency of lysosomal TMEM175 in myeloid macrophages exerts anti-tumor immunity via inflammasome and cross-presentation pathway - PubMed
3 months ago
- Deficiency of lysosomal TMEM175 in myeloid macrophages enhances anti-tumor immunity.
- TMEM175 knockout in macrophages inhibits tumor growth and metastasis by promoting M1-like polarization and reducing M2-like polarization.
- Enhanced recruitment and activation of T cells and NK cells in the tumor microenvironment (TME) due to TMEM175 deficiency.
- Anti-tumor effects are mediated via inflammasome (caspase-1, IL-1β, IL-18) and cross-presentation pathways.
- Tmem175-/- BMDMs show improved tumor antigen cross-presentation, further enhanced by IL-1β and IL-18.
- NLRP3 inflammasome activation in Tmem175-/- BMDMs occurs through lysosomal permeabilization and cathepsin B leakage.
- Tmem175-/- mice exhibit better responsiveness to anti-PD-1 therapy.
- TMEM175 is identified as a potential target for cancer immunotherapy.
Four-Year outcomes of first-line Nivolumab plus ipilimumab for 6 months versus continuation in patients with advanced non-small-cell lung cancer Results of the randomized IFCT-1701 "DICIPLE" Phase III
3 months ago
- Study evaluated 6-month nivolumab-ipilimumab (IO) therapy versus continuation in metastatic non-small-cell lung cancer (mNSCLC) patients with disease control.
- Randomized trial included 265 treatment-naïve mNSCLC patients; 71 were randomized to continuation (36) or experimental (stop and resume at progression, 35) arms.
- Median progression-free survival (PFS) was 18.7 months in the continuation arm vs. not reached in the experimental arm.
- Median overall survival (OS) was 55.5 months in the continuation arm vs. not reached in the experimental arm.
- 18-month OS rates were 80.6% (continuation) and 93.8% (experimental).
- Higher grade 3-5 treatment-related adverse events in the continuation arm (54.3% vs. 23.5%).
- Quality of life (QoL) deterioration was delayed in the experimental arm (median time NR vs. 15.5 months in continuation).
- Conclusion: Stopping IO at 6 months showed no survival harm, reduced severe adverse events, and delayed QoL deterioration.
Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649 - PubMed
3 months ago
- Nivolumab plus chemotherapy shows sustained overall survival (OS) and progression-free survival (PFS) benefits in patients with PD-L1 CPS ≥5 after 5 years.
- Five-year OS rates were 16% for nivolumab plus chemotherapy vs. 6% for chemotherapy alone in PD-L1 CPS ≥5 patients.
- Objective response rate was higher with nivolumab plus chemotherapy (58%) compared to chemotherapy alone (46%).
- Survival benefits were maintained across different PD-L1 expression levels (CPS ≥1, CPS ≥10) and all randomized patients.
- Grade 3/4 treatment-related adverse events occurred in 60% of nivolumab plus chemotherapy patients vs. 45% with chemotherapy alone.
- No new safety concerns were identified after long-term follow-up.
- Nivolumab plus chemotherapy is reinforced as a standard first-line treatment for PD-L1 positive gastroesophageal adenocarcinoma.
pH/ROS-Responsive Injectable Hydrogel Co-Loaded with B7-H3 Blocker and NETs Suppressor Boosts OSCC Synergistic Immunotherapy - PubMed
3 months ago
- Injectable pH/ROS-responsive hydrogel co-loaded with B7-H3 blocker (enoblituzumab) and NETs suppressor (Cl-amidine) for OSCC immunotherapy.
- Hydrogel formed by boronic ester bonds and Schiff base linkages ensures precise drug release in acidic, high-ROS tumor microenvironment (TME).
- Localized intratumoral delivery avoids systemic toxicity and off-target effects, enabling high intratumoral drug accumulation.
- Significant tumor growth suppression in orthotopic and subcutaneous OSCC models compared to monotherapies or controls.
- Synergistic TME reprogramming: Cl-amidine inhibits NETs to enhance T-cell infiltration, enoblituzumab restores cytotoxic T-cell function and boosts antibody-dependent cellular cytotoxicity.
- Suppression of OSCC invasion and metastasis by inhibiting B7-H3 and NETs, reversing epithelial-mesenchymal transition (EMT).
- Excellent biocompatibility with no systemic toxicity observed.
UBE2T-Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation-Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer - PubMed
3 months ago
- UBE2T promotes p53 degradation, enhancing glycolysis in pancreatic ductal adenocarcinoma (PDAC).
- Excessive lactate from glycolysis leads to histone H3 lysine 18 lactylation (H3K18la) in cancer-associated fibroblasts (CAFs).
- Lactylation activates CAFs, causing extracellular matrix (ECM) densification and reduced immunotherapy efficacy in PDAC.
- UBE2T inhibition with pentagalloylglucose (PGG) disrupts lactate crosstalk, reduces ECM deposition, and increases CD8+ T cell infiltration.
- Combining PGG with anti-PD-1 therapy improves outcomes in PDAC models.
- Targeting UBE2T offers a potential strategy to enhance immunotherapy effectiveness in PDAC.
NK Cell Activation by Platinum Boosts Immunotherapy in HR+/HER2- Breast Cancer - PubMed
3 months ago
- Immunotherapy has limited efficacy in HR+/HER2- breast cancer.
- Activated NK cells correlate with better anti-PD-(L)1 responses in HR+/HER2- breast cancer.
- Preclinical models show immunotherapy enhances NK cell cytotoxicity and immunomodulatory functions, reducing tumor growth.
- Platinum drugs enhance NK cell cytotoxicity, possibly via the NF-κB pathway, synergizing with immunotherapy.
- Clinical cohort analysis reveals increased activated NK cells in tumors after platinum-based chemotherapy.
- The study highlights NK cells' role in immunotherapy response and platinum's potential to boost efficacy.
TTF-1 expression in lung adenocarcinoma: clinicopathologic, genomic, and immunophenotypic correlates and outcomes to immunotherapy-based treatments and KRASG12C inhibitors - PubMed
3 months ago
- TTF-1 expression in lung adenocarcinoma (LUAD) is negative (TTF-1Neg) in 15-20% of cases, associated with worse outcomes.
- TTF-1Neg LUAD is linked to more frequent tobacco use, lower PD-L1 expression, and mutations in STK11, KEAP1, SMARCA4, NKX2-1, CDKN2A, and KRAS.
- Patients with metastatic TTF-1Neg LUAD had worse responses to immune checkpoint inhibitors, chemo-immunotherapy, durvalumab, and KRASG12C inhibitors compared to TTF-1Pos cases.
- TTF-1Neg cases showed lower objective response rates (ORR), shorter median progression-free survival (mPFS), and shorter median overall survival (mOS) across treatments.
- TTF-1 negativity identifies a subset of LUAD with poor outcomes to various therapies, including immunotherapy and KRASG12C inhibitors.
The use of advanced machine learning to predict outcomes after atezolizumab plus bevacizumab for advanced hepatocellular carcinoma: a retrospective cohort study - PubMed
3 months ago
- Study focused on using advanced machine learning to predict outcomes for advanced hepatocellular carcinoma (HCC) patients treated with atezolizumab plus bevacizumab.
- Retrospective cohort study conducted across 24 centers in eight countries, involving 774 patients after exclusions.
- Seven supervised machine learning models combined with 13 feature selection techniques were trained on 44 baseline clinical variables.
- Ensemble models for overall survival (OS) and progression-free survival (PFS) outperformed traditional clinical benchmarks.
- Patients were stratified into low-risk and high-risk groups, with significant differences in median OS and PFS between groups.
- The study suggests that machine learning models can improve personalized treatment strategies for HCC patients.
Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB-IV melanoma (KEYVIBE-010): a randomised, double-blind, phase 3 study - PubMed
3 months ago
- The study evaluated vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB-IV melanoma.
- A total of 1402 participants were randomly assigned to receive either the coformulated treatment or pembrolizumab alone.
- At the first interim analysis, the median study follow-up was 4.2 months, with no significant difference in recurrence-free survival between the two groups.
- The hazard ratio for recurrence-free survival was 1.25 (95% CI 0.9-1.8), indicating no additional clinical benefit from the coformulated treatment.
- Common grade 3 or higher treatment-related adverse events included adrenal insufficiency, hepatitis, rash, maculopapular rash, and pruritus.
- Treatment-related serious adverse events occurred in 11% of the coformulated group and 4% of the pembrolizumab alone group.
- The study was discontinued based on prespecified futility criteria, concluding that pembrolizumab monotherapy remains the standard of care for resected high-risk melanoma.
Natural killer and CAR-NK cell therapies in urological cancers: Progress, mechanistic lessons from CAR-T, and future directions - PubMed
3 months ago
- Review of NK and CAR-NK cell therapies for urological cancers (renal cell carcinoma, bladder cancer, prostate cancer).
- NK cells offer advantages like 'missing-self' recognition and ADCC, with lower risks of cytokine release syndrome and graft-versus-host disease compared to CAR-T cells.
- Coverage of conventional NK strategies, CAR-NK engineering to tackle the immunosuppressive tumour microenvironment, and preclinical/clinical advances with antigens like CAIX, CD70, PSMA, and nectin-4.
- CAR-NK therapy is a promising 'off-the-shelf' modality, but success in solid tumours depends on solving challenges like in vivo persistence, tumour homing, and resistance to immunosuppression.
DSG2+ Cancer Stem Cells Co-Located With FAP+ Myofibroblasts in the Tumor Boundary That Determines the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer - PubMed
3 months ago
- DSG2+ cancer stem cells (CSCs) are co-located with FAP+ myofibroblasts (myCAFs) at the tumor boundary in non-small cell lung cancer (NSCLC).
- DSG2 is identified as a dominant marker for CSCs, associated with chemotherapy resistance and response to EGFR tyrosine kinase inhibitors.
- Spatial mapping shows DSG2+ CSCs enriched at tumor margins, co-localizing with FAP+ myCAFs that express MMP9 and MMP12.
- myCAFs enhance CSC-associated phenotypes in DSG2-high tumor cells in an MMP-dependent manner, contributing to therapeutic resistance.
- The study integrates single-cell RNA sequencing and spatial transcriptomics to define CSC-associated phenotypes in NSCLC.

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#immunotherapy

2026 Update on the Management of Diffuse Large B-Cell Lymphoma - PubMed

Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment - PubMed

Atlas-guided discovery of transcription factors for T cell programming - PubMed

Noninvasive imaging-based assessment of tumor-associated neutrophils for prognosis and immunotherapy response in gastric cancer: a multicenter study - PubMed

ITGB1 Regulates Triple-Negative Breast Cancer Development by Modulating the Tumor Microenvironment - PubMed

Randomized Trial Links Time of Day to Immunotherapy Success - PubMed

Oncolytic virus OH2 induces PD-L1 upregulation via NF-κB signaling and synergizes with anti-PD-L1 therapy in prostate cancer through a targeted extracellular vesicle delivery system - PubMed

Kitasamycin overcomes ferroptosis and immunotherapy resistance by targeting the HUWE1-NCOA4-FTH1 Axis - PubMed

Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy - PubMed

Deficiency of lysosomal TMEM175 in myeloid macrophages exerts anti-tumor immunity via inflammasome and cross-presentation pathway - PubMed

Four-Year outcomes of first-line Nivolumab plus ipilimumab for 6 months versus continuation in patients with advanced non-small-cell lung cancer Results of the randomized IFCT-1701 "DICIPLE" Phase III

Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649 - PubMed

pH/ROS-Responsive Injectable Hydrogel Co-Loaded with B7-H3 Blocker and NETs Suppressor Boosts OSCC Synergistic Immunotherapy - PubMed

UBE2T-Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation-Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer - PubMed

NK Cell Activation by Platinum Boosts Immunotherapy in HR+/HER2- Breast Cancer - PubMed

TTF-1 expression in lung adenocarcinoma: clinicopathologic, genomic, and immunophenotypic correlates and outcomes to immunotherapy-based treatments and KRASG12C inhibitors - PubMed

The use of advanced machine learning to predict outcomes after atezolizumab plus bevacizumab for advanced hepatocellular carcinoma: a retrospective cohort study - PubMed

Vibostolimab coformulated with pembrolizumab versus pembrolizumab alone as adjuvant therapy for high-risk stage IIB-IV melanoma (KEYVIBE-010): a randomised, double-blind, phase 3 study - PubMed

Natural killer and CAR-NK cell therapies in urological cancers: Progress, mechanistic lessons from CAR-T, and future directions - PubMed

DSG2+ Cancer Stem Cells Co-Located With FAP+ Myofibroblasts in the Tumor Boundary That Determines the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer - PubMed