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In the CheckMate 142 study, nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) was shown to induce durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Here, the authors perform exploratory biomarker analysis of the CheckMate 142 study.

The control of translation during mitosis has an important role in cancer cell biology. Here the authors report that in mitotically arrested cancer cells, redistribution of ribosomes towards upstream open reading frames results in enhanced presentation of immunogenic peptides on cancer cell surface.

Vallentgoed et al. integrate clinical and multiomic data from persons with matched initial and recurrent IDH-mutant astrocytomas to identify progression-associated mechanisms and report a DNA methylation-based signature associated with survival.

Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.

The van der Waals MA₂Z₄ materials are a rapidly growing class of 2D materials with diverse electronic phases. This Review explores the structure, synthesis, properties and diverse applications of the emerging MA₂Z₄ family, highlighting their potential across electronics, catalysis and energy storage.

Silicate rock weathering represents a negative feedback mechanism that regulates atmospheric CO₂ levels on geological timescales. Here, the authors show that a diminished silicate weathering feedback may have set the stage for greenhouse warming and ocean acidification during the Middle Eocene, ~40 million years ago.

Function elements are key components for nanochannel systems for artificial regulation of ion transport. Here, the authors investigate the independent role of function elements at the outer surface of nanochannel systems, without function elements at inner walls, in promoting osmotic energy conversion and biochemical sensing.

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.

Fungal diseases threaten crops worldwide. By resolving the cryo-EM structure of fungal succinate dehydrogenase, researchers designed an inhibitor with broad antifungal activity, strong field performance, and reduced environmental toxicity.

In the secondary endpoint analysis of the phase 3 SONIA trial, circulating tumor DNA (ctDNA) analysis showed that a pretreatment aneuploidy-based high ctDNA level in patients with advanced breast cancer was associated with benefit from first-line treatment with CDK4/6 inhibitors.

While the emergence of immune checkpoint inhibitors has improved cancer patient outcomes, efficacy in high-grade serous ovarian cancer (HGSOC) is limited. Here, the authors report a phase 2 clinical trial investigating immune activation and efficacy of neoadjuvant pembrolizumab administered after one cycle of neo-adjuvant chemotherapy in patients with untreated stage IV HGSOC.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

The phase 3 SONIA trial challenges the benefits of using cyclin-dependent kinase 4 and 6 inhibitors as a first-line compared with second-line treatment.

This large integrated analysis of the KRAS^G12C inhibitor sotorasib clinical efficacy biomarkers from the phase 2 CodeBreaK 100 and phase 3 CodeBreaK 200 trials shows that low expression of TTF-1 and high expression of NRF2 determine anti-tumor efficacy of sotorasib in non–small-cell lung cancer.

A combination of real-world evidence and a reanalysis of phase 3 clinical trial data unveils KRAS codon G12 mutations as a biomarker of resistance to trifluridine/tipiracil in metastatic colorectal cancer.

A preinfusion circulatory inflammation biomarker-based signature predicts the likelihood of treatment failure in patients with non-Hodgkin lymphoma who were treated with CAR-T cell therapy, with an inflammatory cluster assignment being prognostic of clinical response and survival outcomes.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Tumor-derived soluble PD-L1 drives immune checkpoint inhibitor (ICI) resistance and has recently been reported to be removed by therapeutic plasma exchange (TPE). Here, the authors report a phase I clinical trial investigating the combination of radiotherapy, TPE, and ICI rechallenge in patients with ICI-refractory metastatic melanoma with high PD-L1.

Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.

A framework for building foundation models using diverse patient data can enhance survival prediction and provide interpretable insights into treatment response. Here, the authors show that their approach outperforms existing methods while integrating generative and interpretable modules to reveal clinically relevant biological insights.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

In an analysis of adult patients with hematologic malignancies who received anti-CD19 chimeric antigen receptor T cell therapy, baseline gut microbiome composition was correlated with clinical response and treatment with broad-spectrum antibiotics in the four weeks prior to infusion was associated with worse survival and increased neurotoxicity.

Identification of biomarkers to stratify patients who might benefit from treatment is needed to optimize targeted therapies. Here, based on an analysis of the RANGE trial (NCT02426125), the authors report potentially predictive biomarkers for survival benefit in patients with platinum-refractory advanced urothelial carcinoma treated with the anti-VEGFR2 monoclonal antibody ramucirumab.

Longitudinal genomic and transcriptomic profiling of 1,143 patients with multiple myeloma by the Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study yields an improved copy number and gene expression subtype scheme, most notably a high-risk proliferative subtype associated with complete loss of RB1 or MAX.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Countries are using hospital admission policies that prioritize patients with COVID-19 during the pandemic. The authors propose an alternative open-source framework to optimally schedule hospital care for all diseases and patients that can save life years overall.

The ultrathin thickness, high pore density and short interpore distance of a COF monolayer endow an extremely low membrane resistance and strong pore–pore coupling, which greatly improves the membrane-based osmotic power generation.

In this genomic analysis of peripheral blood samples of the phase 3 CheckMate-067 trial of ipilimumab (IPI) versus nivolumab (NIVO) versus ipilimumab and nivolumab (IPI-NIVO) in melanoma, the status of certain mitochondrial haplogroups in patients was associated therapeutic resistance to NIVO or IPI-NIVO, a finding validated in an independent cohort.

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically use tumor-specific mutations that may not be detected in many patients. Here, the authors develop a tumor-independent and mutation-independent approach (DELFI-TF) to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

Immunotherapy using dendritic cell (DC)-based vaccination has been exploited in the clinic for cancer treatment. Here the authors report the results of a randomized, placebo-controlled, phase 3 trial of adjuvant blood-derived DC cell-based therapy in patients with stage IIIB and IIIC melanoma.

In this phase 2 basket trial, patients with heavily pretreated HER2-mutated metastatic breast cancer received the small-molecule HER2 inhibitor tucatinib and anti-HER2 trastuzumab, leading to encouraging clinical response rates.

The Great Oxidation Event (GOE) is considered to have occurred at 2.33–2.32 Ga based on the last occurrence of MIF-S in South Africa. Here, based on sulphur isotope analysis of samples from Western Australia, the authors show preservation of MIF-S beyond 2.31 Ga and call for a re-evaluation of GOE timing.

Poeck and colleagues identify a microbiome signature in patients receiving allogenic stem cell transplantation, which is associated with protective immune-modulatory metabolites, improved survival and less transplant-related mortality.

Roesch and colleagues use clinical datasets and mouse models of BRAF-mutant melanoma to reveal a role for IL-17A in positive responses to anti-PD-1 and anti-CTLA-4 therapy, which they also link to infiltrating neutrophils.

The immune response of immunotherapy in colorectal cancer remains low and new adjuvant targets are in demand. By in vivo CRISPR-Cas9 screening that targets membrane and secreted proteins genes, the authors identify that disrupting MBTPS1 in tumor cells upregulates STAT1-transcribed chemokines, promotes CXCR3⁺ CD8 T cells infiltration and potentiates anti-PD-1 therapy.

Ting and colleagues report the safety and efficacy of combined radiation and immunotherapy in a phase II trial on patients with MSS colorectal or pancreatic cancer and observe that disease control correlates with higher repetitive RNA transcription.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.