Featured
-
-
Article
| Open AccessTumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial
Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. This trial evaluates the combination of the ATR inhibitor, ceralasertib, with palliative radiotherapy in 27 patients with advanced solid tumors.
- Magnus T. Dillon
- , Emmanuel C. Patin
- & Kevin J. Harrington
-
Article
| Open AccessAutocrine interferon poisoning mediates ADAR1-dependent synthetic lethality in BRCA1/2-mutant cancers
The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the authors report that BRCA1/2 and ADAR1 are synthetic lethal, showing that ADAR1 depletion in BRCA1-mutant cells causes autocrine interferon poisoning
- Roman M. Chabanon
- , Liudmila Shcherbakova
- & Sophie Postel-Vinay
-
Article
| Open AccessEpigenomic diagnosis and prognosis of Acute Myeloid Leukemia
The prognostic and diagnostic roles of DNA methylation in acute myeloid leukemia remains to be explored. Here, the authors develop DNA methylation-based models for the prediction of five-year survival and clinical molecular subtypes in both pediatric and adult test cohorts.
- Francisco Marchi
- , Vivek M. Shastri
- & Jatinder K. Lamba
-
Article
| Open AccessInhibition of HDAC6 alters fumarate hydratase activity and mitochondrial structure
Here they show that HDAC6 inhibition regulates fumarate hydratase (FH), disrupts mitochondria, increases fumarate, and causes cancer cell death. This suggests that HDAC6 inhibition could be a strategy to target tumour metabolism indirectly.
- Andrew Roe
- , Catríona M. Dowling
- & Tríona Ní Chonghaile
-
Article
| Open AccessLongitudinal circulating tumor DNA analysis during treatment of locally advanced resectable gastric or gastroesophageal junction adenocarcinoma: the PLAGAST prospective biomarker study
Despite pre- and post-operative treatment, patients with locally advanced resectable gastric/gastroesophageal junction adenocarcinomas have a high recurrence risk. Here, the authors analyse a prospective cohort of patients and find ctDNA status is correlated with survival outcomes.
- Aziz Zaanan
- , Audrey Didelot
- & Pierre Laurent-Puig
-
Article
| Open AccessMachine-learning driven strategies for adapting immunotherapy in metastatic NSCLC
The approval of first line immune checkpoint blockade (ICB) has improved outcomes for patients with metastatic non-small cell lung cancer (mNSCLC), however, whether patients would benefit more from ICB alone or alongside chemotherapy is unclear. Here, the authors develop a machine-learning based approach to help guide individual treatment selection patients with mNSCLC.
- Maliazurina B. Saad
- , Qasem Al-Tashi
- & Jia Wu
-
Article
| Open AccessMetabolism archetype cancer cells induce protumor TREM2+ macrophages via oxLDL-mediated metabolic interplay in hepatocellular carcinoma
Tumour cells can alter the function and metabolism of immune cells to reduce anti-tumour responses. Here the authors use single cell sequencing of HCC and show three tumour archetypes; metabolism, inflammation and stemness and the metabolism archetype are found in association with TREM+ macrophages which restrict immune cell infiltration into the tumour microenvironment.
- Tianhao Chu
- , Guiqi Zhu
- & Yinghong Shi
-
Article
| Open AccessTransdifferentiation of tongue muscle cells into cancer-associated fibroblasts in response to tongue squamous cell carcinoma
Tongue Squamous Cell Carcinoma (TSCC) is a subtype of head and neck cancer with poor prognosis. Here, the authors show that TSCC influences the transdifferentiation of tongue muscle cells into cancer-associated fibroblasts, transforming the tumor microenvironment into a tumor-supporting microenvironment.
- Weifan Lin
- , Wuheng Huang
- & Yan Zhang
-
Article
| Open AccessST2/IL-33 axis blockade inhibits regulatory T cell cytotoxicity towards CD8 T cells in the leukemic niche
Therapeutic checkpoint for acute myeloid leukemia requires further investigations. The authors here identify ST2+ Treg cells facilitate AML growth by inducing CD8+ T cell depletion and exhaustion, while targeting ST2 by antibodies depletes ST2+ Treg cells and improves AML prognosis.
- Hua Jiang
- , Denggang Fu
- & Sophie Paczesny
-
Article
| Open AccessConstitutive inflammation and epithelial-mesenchymal transition dictate sensitivity to nivolumab in CONFIRM: a placebo-controlled, randomised phase III trial
The sensitivity of mesothelioma to the treatment of immune checkpoint blockade remains elusive. Here this group reports a double blind, placebo-controlled, randomized phase III trial of PD1 inhibitor (Nivolumab) on 332 patients with relapsed mesothelioma, and to uncover determinants of efficacy.
- Dean A. Fennell
- , Kayleigh Hill
- & Gareth O. Griffiths
-
Article
| Open AccessThe invasion phenotypes of glioblastoma depend on plastic and reprogrammable cell states
Glioblastoma (GBM) is a common brain cancer characterized by local invasion. Here, authors identify regulators of GBM cell differentiation states and invasion routes, demonstrating that targeting these regulators alters invasion patterns and extends survival in mouse models.
- Milena Doroszko
- , Rebecka Stockgard
- & Sven Nelander
-
Article
| Open AccessNanomechanical binding mechanism of ligands drives agonistic activity
Monoclonal antibodies and ligands targeting CD40 exhibit diverse agonistic and antitumor activities that are influenced by their design. Here, the authors identify mechanistic differences between clinically relevant anti-CD40 subclasses and CD40L, focusing on the dynamics and strengths of multi-bond formation at the single-molecule level.
- Hannah Seferovic
- , Patricia Sticht
- & Peter Hinterdorfer
-
Article
| Open AccessCell-free DNA testing for the detection and prognosis prediction of pancreatic cancer
Pancreatic cancer detection can be challenging, and is often diagnosed at a late stage. Here, the authors present a cfDNA-based liquid biopsy model that enables early detection and prognosis prediction of pancreatic cancer.
- Jianmin Wu
- , Xiongfei Xu
- & Lei Chen
-
Article
| Open AccessThe tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy
Tumor draining lymph nodes are essential for immunotherapy efficacy in head and neck squamous cell carcinoma (HNSCC). Here, the authors show that sequential tumor-directed radiotherapy and PD-1 inhibition and migratory CCR7+ dendritic cells are required for complete and durable tumor responses in HNSCC.
- Robert Saddawi-Konefka
- , Riyam Al Msari
- & Joseph A. Califano
-
Article
| Open AccessPersonalized risk stratification in colorectal cancer via PIANOS system
Current prognostic biomarkers for colorectal cancer (CRC) tend to lack generalisability across different cohorts and platforms. Here, the authors introduce PIANOS, a classifier for stratifying CRC patients into distinct risk groups across different platforms and cohorts, which allows predicting clinical outcomes and therapies.
- Du Cai
- , Haoning Qi
- & Xiaojian Wu
-
Article
| Open AccessDKN-01 and tislelizumab as second-line therapy in DKK1-high gastroesophageal adenocarcinoma: DisTinGuish trial part B
Dickkopf-related protein 1 (DKK1) is a secreted protein associated with poorer outcomes in patients with gastric cancer. Here, the authors report part B of the DisTinGuish phase II trial reporting the safety and efficacy of DKN-01 (DKK1 neutralising antibody) in combination with tislelizumab (anti-PD-1) in patients with advanced gastric/gastoesophageal junction cancer and elevated DKK1 expression.
- Keun-Wook Lee
- , Devalingam Mahalingam
- & Samuel J. Klempner
-
Article
| Open AccessImaging of macrophage accumulation in solid tumors with ultrasound
Imaging macrophage trafficking in solid tumors has implications for cancer diagnosis and prognosis. by labeling macrophages with lipid-shelled microbubbles in combination with ultrasound, the authors here achieve nondestructive in vivo intravenously administrated macrophage imaging at single cell level with 100 µm resolution till 8 h in solid tumors in rodents.
- Ashley Alva
- , Chulyong Kim
- & Costas Arvanitis
-
Article
| Open AccessJAK2 inhibition mediates clonal selection of RAS pathway mutations in myeloproliferative neoplasms
The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.
- Nabih Maslah
- , Nina Kaci
- & Lina Benajiba
-
Article
| Open AccessTumor vessel-adaptable adhesive and absorbable microspheres for sustainable transarterial chemoembolization therapy
Transarterial chemoembolization (TACE) is a common clinical intervention used for unresectable liver tumors, but conventional embolic microspheres generally exhibit slack vascular stacking and suboptimal drug release. Here, Guo et al. report tumor vessel-adaptable, adhesive, and absorbable microspheres (3Asphere) for sustained TACE therapy of liver tumors.
- Jiakun Guo
- , Jintao Huang
- & Zhiyuan Zhong
-
Article
| Open AccessYY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer in mice
Immune check point therapies have not been successful for prostate cancers, but the underlying mechanisms are unclear. Here the authors show that a transcription factor, YY1, may promote the SUMOylation and stability of HIF-1α to suppress anti-tumor immunity, while targeting YY1 helps improve tumor control, in mouse prostate cancer models.
- Wenchao Li
- , SaiSai Chen
- & Bin Xu
-
Article
| Open AccessImmune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma
Two BCMA-targeted CAR T products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), have been approved for the treatment of multiple myeloma (MM). Here the authors report distinct expansion, phenotype, function, and toxicity of cilta-cel vs. ide-cel CAR T cells in a realworld cohort of patients with MM.
- Djordje Atanackovic
- , Tim Luetkens
- & Mehmet H. Kocoglu
-
Article
| Open AccessMast cells boost anti-tumor potency of MAIT cells via inflammasome-dependent secretion of IL-18
The immunomodulatory functions of mast cells (MCs) within the tumor microenvironment are elusive. Here, the authors present a transcriptomic characterization of LUAD-infiltrating MCs and identify a proinflammatory subset that contributes to the activation of cytotoxic MAIT cells by secreting IL-18 via NRLP3 activation and pyroptosis, ultimately boosting anti-tumor immunity.
- Fanfan Fan
- , Jun Wang
- & Haiquan Chen
-
Article
| Open AccessSingle atom engineering for radiotherapy-activated immune agonist prodrugs
On-target, off-tumour toxicity is a major concern in immunotherapy. Here, aided by computer docking analysis, the authors introduce a single oxygen atom into the TLR7/8 agonist R848, generating a radiotherapy-activatable prodrug agonist that in mice helps mitigate systemic toxicity while triggering effective anti-tumor immunity responses upon radiation.
- Zexuan Ding
- , Xiaozhe Yin
- & Zhibo Liu
-
Article
| Open AccessEpstein Barr virus antibody and cancer risk in two prospective cohorts in Southern China
Epstein-Barr virus is associated with increased cancer risk. Here, the authors analysed two population-based prospective cohorts in Southern China to examine the association between increased seropositivity and the risk of multiple cancer types.
- Ming-Fang Ji
- , Yong-Qiao He
- & Wei-Hua Jia
-
Article
| Open AccessRadiation therapy results in preferential tumor antigen-specific lymphodepletion in head and neck cancer
Combining radiation therapy (RT) with immunotherapy has had limited therapeutic benefits in the treatment of head and neck cancer (HNSCC). Here, the authors present a multi-omics analysis of patient biopsies pre- and post- hypofractionated RT and uncover RT-mediated depletion of tumor-reactive CD8+ T cells as the underlying cause of immunologic radioresistance in HNSCC.
- Joseph Zenga
- , Musaddiq J. Awan
- & Heather A. Himburg
-
Article
| Open AccessDual TIGIT and PD-1 blockade with domvanalimab plus zimberelimab in hepatocellular carcinoma refractory to anti-PD-1 therapies: the phase 2 LIVERTI trial
Therapies targeting PD-1/PD-L1 have become first line therapies for patients with hepatocellular carcinoma (HCC) but response rates remain limited. Here, the authors report a cohort from the LIVERTI basket investigating domvanalimab (Fc-silentanti-TIGIT) and zimberelimab (anti-PD1) in immunotherapy refractory advanced HCC.
- David Hsiehchen
- , Radhika Kainthla
- & Hao Zhu
-
Article
| Open AccessIdentification of the Notch ligand DLK1 as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma
Adrenocortical carcinoma (ACC) has limited treatment options and few tumor-specific targets. Here the authors report that the Notch ligand DLK1 is highly expressed in ACC acting as a regulator of tumor cell plasticity and chemoresistance, and that DLK1 can be targeted with an antibody drug conjugate.
- Nai-Yun Sun
- , Suresh Kumar
- & Nitin Roper
-
Article
| Open AccessNeoadjuvant ARX788 plus pyrotinib versus trastuzumab, pertuzumab, docetaxel and carboplatin for HER2-positive breast cancer: a randomised phase 2b trial
Combining antibody drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) targeting HER2 has been shown to improve efficacy in patients with advanced HER2+ breast cancer. Here, the authors report a randomised phase 2b trial comparing neoadjuvant ARX788 (HER2 ADC) plus pyrotinib (HER1, HER2 and HER4 TKI) against neoadjuvant standard of care (docetaxel, carboplatin, trastuzumab, and pertuzumab) for the treatment of HER2+ breast cancer.
- Nan Niu
- , Jinqi Xue
- & Caigang Liu
-
Article
| Open AccessDual asparagine-depriving nanoparticles against solid tumors
Depletion of circulatory asparagine (Asn) by L-asparaginase (ASNase) has been used for clinical treatment of leukemia. Here this group develops core-shell structured cascade-responsive nanoparticles for sequential modulation of exogenous Asn supply and endogenous Asn production, thereby achieving the amino acid depletion therapy against solid tumors.
- Yubo Shen
- , Huifang Wang
- & Xiaoyuan Ji
-
Article
| Open AccessIntraindividual epigenetic heterogeneity underlying phenotypic subtypes of advanced prostate cancer
The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.
- Kei Mizuno
- , Sheng-Yu Ku
- & Himisha Beltran
-
Article
| Open AccessHistone serotonylation promotes pancreatic cancer development via lipid metabolism remodeling
The neurotransmitter serotonin regulates cancer through receptor-signaling activation, but also epigenetics mechanisms by serotonylation. Here, the authors show that histone serotonylation promotes pancreatic cancer progression by upregulating stearoyl-CoA desaturase (SCD), which remodels lipid metabolism, suggesting a potential target for therapy.
- Sang Lin
- , Sheng Tan
- & Xiaodong Zhao
-
Article
| Open AccessDeep learning assessment of metastatic relapse risk from digitized breast cancer histological slides
Early breast cancer is often responsive to treatment, however, long-term prognosis is variable. Here, the authors utilise a deep learning model to predict metastasis free survival using digitised tumour slides.
- I. Garberis
- , V. Gaury
- & M. Lacroix-Triki
-
Article
| Open AccessGenomic landscape of virus-associated cancers
Virus-associated cancers remain prevalent worldwide, particularly in developing countries. Here, the authors analyse epidemiological, genetic, and therapeutic trends across nine types of virus-associated cancers, finding that virus-positive tumours are associated with specific demographic and mutational features as well as treatment response rates.
- Yoonhee Nam
- , Karen Gomez
- & Raul Rabadan
-
Article
| Open AccessWhole genome and transcriptome profiling in advanced pancreatic cancer patients on the COMPASS trial
The COMPASS trial is a prospective observational study seeking to establish biomarkers in advanced pancreatic cancer through in-depth profiling prior to commencing chemotherapy. Here, the authors report the final data for the complete cohort of 268 patients enrolled in the COMPASS trial.
- Jennifer J. Knox
- , Gun Ho Jang
- & Grainne M. O’Kane
-
Article
| Open AccessAn mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy
Hydrogel materials have emerged as versatile platforms for biomedical applications. Here this group reports an mRNA lipid nanoparticle-incorporated microgel matrix for immune cell recruitment/antigen expression and presentation/cellular interaction thereby eliciting antitumor efficacy with a single dose.
- Yining Zhu
- , Zhi-Cheng Yao
- & Hai-Quan Mao
-
Article
| Open AccessDivergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer
Tumour evolution and heterogeneity in high grade serous ovarian cancer (HGSOC) remains poorly characterised. Here, the authors investigate the genomic landscape of HGSOC and reveal two distinct evolutionary trajectories associated with clinical outcomes.
- Ailith Ewing
- , Alison Meynert
- & Colin A. Semple
-
Article
| Open AccessEvolutionary regulation of human Fas ligand (CD95L) by plasmin in solid cancer immunotherapy
Fas ligand (FasL) regulates immunotherapeutic cancer-cell death. Here, the authors show a human-specific amino-acid substitution which renders human FasL more susceptible for plasmin cleavage and is relevant for the efficacy of T-cell-based immunotherapies.
- Brice E. N. Wamba
- , Tanmoy Mondal
- & Jogender Tushir-Singh
-
Article
| Open AccessIndividualizing glioma radiotherapy planning by optimization of a data and physics-informed discrete loss
Current treatment plans for brain tumors fail to account for the nuances of diversified individual patient conditions regarding the tumor infiltrating margins in brain tissues. Here this group reports a Fisher-Kolmogorov type physics model inferring the full spatial distribution of tumor cell concentration from available multi-modal imaging on glioblastoma patients for tumor recurrence monitoring.
- Michal Balcerak
- , Jonas Weidner
- & Bjoern Menze
-
Article
| Open AccessHuman cancer-targeted immunity via transgenic hematopoietic stem cell progeny
Therapeutic T cells engineered to recognize tumour antigens are frequently short-lived and acquire unfavourable phenotypes in tumours. Here authors show that a tandem approach using autologous T cells targeted against the tumour antigen NY-ESO-1, followed by transfer of hematopoietic stem cells with the same specificity in the clinical trial NCT03240861, provides a safe and promising therapeutic option.
- Theodore S. Nowicki
- , Nataly Naser Al Deen
- & Antoni Ribas
-
Article
| Open AccessCaffeine enhances antitumor T-cell activity by suppressing kynurenine pathway in colorectal cancer
Coffee has been associated with reduced colorectal cancer incidence. Here, the authors show that caffeine inhibits the kynurenine pathway, boosting CD8+ T-cell immunogenic activity, which impairs colorectal cancer progression and enhances immunotherapy response.
- Yuechen Liu
- , Zhengyu Liu
- & Haijun Deng
-
Article
| Open AccessImmunomics-guided biomarker discovery for human liver fluke infection and infection-associated cholangiocarcinoma
Sensitive diagnostics are needed to detect carcinogenic human liver fluke infections. Sadaow et al. here use an immunomics approach to develop field-deployable tests for diagnosing liver fluke infection and its associated liver cancer.
- Lakkhana Sadaow
- , Rutchanee Rodpai
- & Pewpan M. Intapan
-
Article
| Open AccessUncovering minimal pathways in melanoma initiation
Identifying the sequence of molecular events that leads to melanoma remains challenging. Here, the authors analyse the early stages of melanoma development in mouse models of minimal genetic induction, identifying melanoma emergence with little evidence of consistent DNA mutation or common copy number variation.
- Hui Xiao
- , Jessica Shiu
- & Anand K. Ganesan
-
Article
| Open AccessQuantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding
Understanding the dynamics of how drug resistance originates in cancer remains crucial, but it is not possible to observe them directly. Here, the authors construct a mathematical framework to infer drug resistance dynamics in cancer using lineage tracing and population size data, which is confirmed with experimental evidence and single-cell sequencing.
- Frederick J. H. Whiting
- , Maximilian Mossner
- & Trevor A. Graham
-
Article
| Open AccessAI-Based screening for thoracic aortic aneurysms in routine breast MRI
Routine breast MRI scans provide an opportunity to screen for thoracic aortic aneurysms, which are more fatal in women. Here, the authors show that a fully automated AI tool can screen for these aneurysms using routine breast MRI scans.
- Dimitrios Bounias
- , Tobit Führes
- & Sebastian Bickelhaupt
-
Article
| Open AccessCytoreductive surgery and hyperthermic intrathoracic chemotherapy in thymic epithelial tumors with pleural spread or recurrence: a prospective, single-arm, phase II study
Pleural spread or recurrence of thymic epithelial tumors (TETs) needs further exploration in clinics and there is currently no recognized effective treatment. Here this trial evaluates the perioperative and short-term outcomes of cytoreductive surgery and hyperthermic intrathoracic chemotherapy (S-HITOC) for TETs with pleural spread or recurrence.
- Shuai Wang
- , Xinyu Yang
- & Jianyong Ding
-
Article
| Open AccessIncreased antioxidative defense and reduced advanced glycation end-product formation by metabolic adaptation in non-small-cell-lung-cancer patients
Oxidative stress is known to play a role in lung cancer carcinogenesis with protein cysteines residues being key in redox signaling. Here, the authors discover in lung cancer patients through redox proteomics that there is a higher oxidation of the cysteines of glycolytic and methylglyoxal metabolism enzymes.
- Tamara Tomin
- , Sophie Elisabeth Honeder
- & Ruth Birner-Gruenberger
-
Article
| Open AccessInhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon response via MYC/CDK2/DNMT1 pathway
The function and regulatory mechanism of mRNA acetylation modification in cancer progression remains largely unknown. Here the authors identify that targeting tumor N4-acetylcytidine (ac4C) RNA acetyltransferase NAT10 improves anti-tumor response via MYC/CDK2/DNMT1/dsRNA/type I IFN pathway, and show the synergic anti-tumor effect of NAT10 inhibition with aPD-1.
- Wan-cheng Liu
- , Yi-hong Wei
- & Dao-xin Ma
-
Article
| Open AccessInflammatory diseases and risk of lung cancer among individuals who have never smoked
Inflammatory diseases may play an important role in lung cancer in never-smokers (LCINS) pathogenesis. Here, the authors show that conditions such as GERD or COPD could be considered as part of eligibility criteria for LCINS screening programs in the future.
- Monica E. D’Arcy
- , Ruth M. Pfeiffer
- & Maria Teresa Landi
-
Article
| Open AccessAnlotinib plus toripalimab as a first-line treatment in patients with advanced gastric cancer and performance status 2: the phase II APICAL-GC trial
Patients with gastric cancer often present with poor performance status, limiting both quality of life but also treatment options as they are often excluded from clinical trials. Here, the authors report a phase II trial investigating anlotinib (multi-TKI) plus toripalimab (anti-PD-L1 monoclonal antibody) in treatment-naïve advanced gastric cancer patients with performance status 2.
- Ke Liu
- , Bao-Dong Qin
- & Yuan-Sheng Zang