A large-scale analysis of real-world data in Nature Medicine has revealed racial disparities in the occurrence of immune-related adverse events during cancer immunotherapy. These disparities were not evident in clinical trial data because enrolled patients were mostly white. The study was published online on 15 October 2026.
A perivascular Postn+ mesenchymal subset of thymic stroma, identified by single-cell analysis of human and mouse tissue, proved to be a critical niche for T lymphopoiesis. Depleting these cells, which likely produce the chemokine Ccl19, blocks recruitment of T cell progenitors, and the subset declines with age and after hematopoietic stem cell transplant conditioning. Adoptively transferred Postn+ cells durably engraft the atrophic thymus, recruit early T progenitors, increase T cell neogenesis and improve T cell responses to vaccination; Ccl19-expressing mesenchymal populations give similar effects.
An inhalable exosome system called BEAT co-displays PD-1 and FZD8 in a uniform 1:1 ratio to block PD-L1 and Wnt7b, overexpressed in immune checkpoint inhibitor-resistant melanoma. BEAT recruited and activated CD8+ T cells, reprogramming the tumor microenvironment and producing robust antitumor activity in mouse models of lung metastases, outperforming a linked dual antibody against PD-L1 and Wnt7b in vivo.
Gilead Sciences has licensed three dual-masked T cell engagers for solid tumors from Vir Biotechnology in a deal worth up to $1.87 billion, including $135 million in upfront and near-term payments. The upfront portion comprises $65 million in cash and a $25 million equity stake, plus $45 million in near-term preclinical milestones, with $1.74 billion in additional milestones possible. Vir will run discovery before handing development of promising assets to Gilead; analysts at H.C. Wainwright await VIR-5818 Phase 1 data in HER2-targeted solid tumors by year-end.
On October 14, 2026, the FDA expanded approval of nogapendekin alfa inbakicept-pmln (Anktiva, Altor BioScience, an ImmunityBio subsidiary) with BCG to cover adults with BCG-unresponsive non-muscle invasive bladder cancer with high-grade papillary-only tumors, beyond the prior indication limited to carcinoma in situ. The agency extrapolated efficacy from Cohort A of QUILT-3.032, a single-arm trial of 77 patients, which showed a complete response rate of 62%. The recommended dose is 400 mcg intravesically with BCG weekly for 6 weeks induction, followed by maintenance for up to 37 months.
Ligand-directed lipid nanoparticles (NtLNPs) carrying mRNA transfected up to ~80% of NK cells in vivo in mice with minimal off-target effects, generating CAR NK cells without ex vivo engineering. CD19-targeted CAR NKs completely depleted circulating B cells in healthy mice, CD3-targeted CAR NKs eliminated nearly all autoreactive T cells in autoimmune hepatitis, and NKG2A-targeting versions improved solid tumor efficacy. Human-optimized NtLNPs produced CAR NK cells that regressed two humanized hematologic malignancy models. The work replaces viral, ex vivo CAR manufacturing with a modular in vivo mRNA delivery platform.
Why it matters: It shows nonviral in vivo CAR NK generation, a route around ex vivo viral engineering of cell therapies.
Personalized neoantigen vaccines combined with PD-1 blockade were feasible in patients with high-grade serous ovarian cancer in a phase 1 trial. Many patients mounted tumor-specific immune responses. Cell-free DNA analysis identified putative resistance mechanisms related to antigen presentation. The trial establishes feasibility of this approach in ovarian cancer and points to antigen presentation as a resistance pathway.
Soluble tumour-derived factors, not direct tumour contact, drive early microglial activation: quantitative proteomics showed extensive remodelling of the microglial proteome after exposure to tumour-conditioned media, with coordinated upregulation of MHC-I, PD-L1 and Galectin-9. Flow cytometry in murine and human cell models confirmed increased PD-L1 and MHC-I, and these microglia induced PD-1 and TIM-3 on cocultured T-cells. Single-cell RNA sequencing datasets from brain tumour patients recapitulate the same immune-regulatory program.
FLASH X-rays at 8 Gy, unlike an equal conventional dose-rate dose, triggered a robust abscopal antitumor effect with anti-PD-1 in a bilateral subcutaneous tumor model in mice. The ultrashort dose delivery conserved neutrophil chromatin compaction, inhibiting neutrophil extracellular trap formation and reversing NET-mediated CD8+ T-cell exclusion, while conventional or split-dose FLASH caused chromatin hyper-relaxation and NETosis. Radiation-induced chromatin relaxation in neutrophils emerges as a determinant of radioimmunotherapy outcome.
Both host antibodies and infused antibodies against HIV delay viral rebound after antiretroviral therapy (ART) interruption, according to a secondary analysis of trial data. The finding points to autologous and broadly neutralizing antibodies as components of approaches aimed at durable, ART-free HIV control.
Topology-driven excited-state engineering of conjugated oligomers yields nanoparticles that improve both imaging and therapy. Under 808 nm laser irradiation, TBT-3 nanoparticles showed 2.8-fold enhanced NIR-II fluorescence brightness, 2.7-fold improved photothermal performance, and 7.5-fold increased total ROS generation versus TBT-1. In vivo, TBT-3 nanoparticles enabled high-resolution NIR-II fluorescence imaging and tumor elimination, and phototherapy induced immunogenic cell death, improving efficacy combined with anti-PD-1 blockade.
Why it matters: It links a molecular topology strategy to quantitative gains in NIR-II imaging and phototherapy plus anti-PD-1 synergy.
Armoring CAR T cells with a secreted tenascin-C-targeted single-chain variable fragment (TNC-scFv) enhanced cytotoxicity, persistence, and reduced exhaustion in vitro and in xenograft tumor models. Single-cell transcriptomics showed the approach reprograms the tumor microenvironment toward a CD8+ T cell-enriched, functionally active immune landscape, and humanized tumor models showed robust antitumor responses with minimal systemic toxicity. Combining the armoring with interleukin-2 further increased efficacy while mitigating cytokine-associated toxicity, establishing extracellular matrix-directed armoring as a generalizable strategy for solid tumors.
Why it matters: It offers a generalizable armoring strategy that improves CAR T cell function against solid tumors, where efficacy has been limited.
Hokkaido University researchers, working with an international team led by University of South Florida Health and Tampa General Hospital, have shown that the 30-year-old sphingolipid rheostat model operates in the tumor microenvironment rather than inside cancer cells in metastatic colorectal cancer. Analysis of 574 human colon cancer tissue samples showed that rising sphingosine-1-phosphate and falling long-chain ceramide create a biochemical barrier that excludes cytotoxic T cells. In lab experiments, blocking S1P/S1PR3 let killer T cells attack tumors again, pointing to a combination strategy with immunotherapy.
Why it matters: It explains a mechanism of immunotherapy resistance in metastatic colorectal cancer and identifies a druggable pathway.
Extended follow-up of in vivo BCMA CAR-T (ESO-T01), given without leukapheresis or lymphodepletion to four patients with relapsed/refractory multiple myeloma, shows no new important adverse events beyond the initial report at up to 15 months. One patient maintained stringent complete response for 15 months; median progression-free survival was 4.0 months (range 3.0-15.0). Three patients relapsed or progressed, all with extramedullary involvement, and died during follow-up, indicating limited CAR-T persistence requiring platform optimization.
NECTIN4, the target of enfortumab vedotin (EV), acts as a subtype-dependent determinant of tumor state and antitumor immunity in bladder cancer. Integrating clinical multi-omics, spatial and single-cell immune profiling, and experimental models, the work shows NECTIN4-high basal/squamous muscle-invasive tumors had favorable survival, higher checkpoint inhibitor response rates, and a CD8+ T cell-inflamed microenvironment, with no comparable associations in luminal papillary tumors; NECTIN4-low models were preferentially sensitive to HDAC inhibition.
Tumor-associated neutrophils drive pre-metastatic immunosuppressive bone marrow remodeling in prostate cancer, emerging at the high-risk bone metastatic potential stage and correlating with poor patient prognosis. Tumor-associated systemic IGF1 reprograms marrow neutrophils via IGF1R-MAPK/ERK-KLF4 signaling, and Igf1 perturbation, IGF1R blockade or neutrophil-specific Igf1r deletion reduces bone metastatic progression. An investigator-initiated trial of teprotumumab plus tislelizumab in metastatic castration-resistant prostate cancer provided initial safety data.
A CRISPR screen of 17q-gain genes identified the RNA m6A reader IGF2BP1 as a critical MYCN collaborator in aggressive neuroblastoma, acting through activation of PAICS, a key enzyme in de novo purine biosynthesis. PAICS-mediated nucleotide metabolism sustained purine pools for transcription of replicative stress-responsive genes including CHK1. Pharmacological inhibition of CHK1 activated cGAS-STING signaling, upregulated MHC class I expression, and suppressed tumors synergistically with immune checkpoint blockade.
Why it matters: Defines an actionable IGF2BP1/MYCN-PAICS-CHK1 axis linking 17q-gain and MYCN to a purine-metabolism vulnerability and immunotherapy response.
The FDA approved atezolizumab (Tecentriq, Genentech) in combination with a fluoropyrimidine and oxaliplatin on October 8, 2026, for adjuvant treatment of Stage III mismatch repair deficient colon cancer in patients two years of age and older, with the subcutaneous Tecentriq Hybreza approved for those 12 years and older weighing 40 kg or greater. In the ATOMIC trial of 711 adults and one pediatric patient, the hazard ratio for disease-free survival was 0.50 versus mFOLFOX6 alone, and median DFS was not reached in either arm. Reviews are ongoing at partner agencies under Project Orbis.
Why it matters: FDA approval of atezolizumab plus chemotherapy as adjuvant therapy for Stage III dMMR colon cancer, with a disease-free survival hazard ratio of 0.50.
CD163+ macrophages emerge as the dominant immunosuppressive interaction partner of T cells in neuroblastoma, engaging the TIGIT/PVR/Nectin-2 axis mainly at the tumor edge and in immune cores. Imaging mass cytometry (n=14) and spectral flow cytometry (n=18) on samples from 28 patients revealed T cell-excluded tumor niches and dysfunctional, tissue-resident T cells, with macrophage CD163 and Nectin-2 expression correlating with poor survival. The findings support combining strategies that boost T cell infiltration with blockade of inhibitory signaling.
BATF-expressing effector regulatory CD4+ T cells (eTreg cells) accumulate in high-grade premalignant airway lesions, are clonally related to circulating eTreg cells, and rise in peripheral blood as lesions progress, allowing lung tumorigenesis to be tracked by blood analysis. In mice, carcinogen-driven tumorigenesis triggered the same preinvasive eTreg axis, and PI3Kδ inhibition reduced circulating and pulmonary Treg cells, increased cDC1s, and reduced lung tumour incidence and size. The work provides a theranostic framework for intercepting lung cancer before invasion.
Why it matters: It identifies a blood-trackable eTreg cell circuit and a druggable interception strategy for preinvasive lung cancer.
A New England Journal of Medicine review traces systemic therapy for breast cancer since 2020, covering targeted therapies, antibody-drug conjugates and immunotherapy across biologic subtypes. CDK4/6 inhibitors remain foundational in hormone-receptor-positive, HER2-negative disease, trastuzumab deruxtecan is reshaping HER2-positive treatment, and immune checkpoint inhibitors have improved outcomes in triple-negative breast cancer. Unresolved issues include treatment sequencing, predictive biomarkers, circulating tumor DNA analysis and equitable access to high-cost therapies.
The FDA has released a set of guidance documents for industry and agency staff issued from July to September 2026. The list includes final guidances on blood collection and storage systems for blood components using the buffy coat method, formal PDUFA meetings, cancer clinical trial eligibility criteria on laboratory values, washout periods and performance status, and FAQs for cellular and gene therapy products. Draft guidances cover premarket approval electronic submission templates, potency assessment of active immunotherapy products, container closure systems for drugs, biologicals and biosimilars.
An effector regulatory T cell circuit can be monitored in blood samples to track the development of lung cancer. Blocking this immune network in the preinvasive setting intercepts tumorigenesis, reducing both tumour incidence and size. The work identifies a blood-accessible immune axis that could enable tracking and early intervention before invasive disease.
Why it matters: It links a blood-monitorable regulatory T cell circuit to preinvasive interception of lung tumorigenesis.
RORγ inverse agonism redirected tumour-conditioned emergency myelopoiesis and attenuated established tumour progression in syngeneic tumour models. In treatment-naive gastroesophageal adenocarcinoma patients, elevated circulating neutrophil-to-lymphocyte ratio tracked with circulating RORγ positive neutrophils and tumoural spatial organization of RORγ positive myeloid cells rather than neutrophil abundance. Pharmacologic RORγ inverse agonism altered marrow progenitor composition before tumour-growth divergence and enhanced longitudinal tumour control with PD-L1 blockade, with effects on metastatic establishment depending on tumour conditioning and treatment timing.
A chromatin accessibility atlas of 650 multistage samples from 439 patients traces epigenetic switches across stepwise gastric tumorigenesis, showing that intestinal metaplasia carries a cancer-resembling priming state that licenses tumor initiation. Advanced tumors split into three epigenomic subtypes: proliferative and mesenchymal-inflammatory subtypes respond to neoadjuvant immunotherapy, while the pseudo-gastric subtype is intrinsically drug resistant. FOSL2-driven up-regulation of H+/K+ ATPase transporters sculpts an acidic milieu suppressing CD8+ T cells, and FOSL2 depletion or the acid blocker vonoprazan sensitizes immunotherapy.
Why it matters: It defines an acid-driven immunotherapy-resistant gastric cancer subtype and a clinically available drug, vonoprazan, that reverses it.
Tumors use the transporter SLC52A2 to scavenge vitamin B2 and outcompete T cells, which depend on SLC52A3-mediated B2 uptake. Deprived T cells lose mitochondrial respiration and glutathione regeneration, undergo mitophagy, labile iron accumulation, and lipid peroxidation, and die by ferroptosis. Deleting tumor SLC52A2 restores T cell function in immunocompetent hosts, and B2 supplementation or SLC52A3 overexpression boosts CAR-T antitumor efficacy. High tumoral SLC52A2 correlated with T cell dysfunction and poor survival.
Why it matters: It identifies a specific nutrient-competition mechanism causing T cell ferroptosis and a targetable transporter axis for immunotherapy.
Nature Reviews Drug Discovery has published a review of immune cell engagers as a strategy for deep B cell depletion in autoimmune diseases. It covers their mechanisms, clinical development and next-generation designs, including T cell, natural killer cell and gamma-delta T cell-engaging formats. It also draws lessons from haematological malignancies to improve the efficacy, safety and durability of immune modulation.
A systematic in vivo screen of altered DNA damage response genes in a genome-edited murine model of MSS colorectal cancer shows that DDR defects have pathway-specific effects on PD-1 blockade response. Loss of Brca1, Brca2, Atm and Fanca enhanced anti-PD-1 response, while Atr and Msh6 deficiency predicted poor benefit, and BRCA1 alterations tracked with improved survival in patients from the MSK-IMPACT cohort. Pre-treatment with pharmacologic ATM inhibition enhanced the antitumor activity of PD-1 blockade in MSS colorectal cancer.
In 1,038 patients with resectable stage IIIB-D melanoma treated across 26 sites, neoadjuvant immune checkpoint inhibitors yielded 5-year recurrence-free survival of 61.0% with PD-1 alone and 73.9% with PD-1 plus another immuno-oncology agent, versus 37.4% with BRAF/MEK inhibitors. Patients achieving a major pathological response had 5-year overall survival of 98.8% and 97.9%, respectively, and gained no benefit from adjuvant ICI continuation. The results define long-term outcomes by regimen and response status.
Why it matters: It quantifies 5-year survival by neoadjuvant regimen and shows adjuvant ICI adds nothing after major pathological response.
The American Association for Cancer Research's Cancer Progress Report 2026 finds that 71% of people with cancer in the United States now live at least five years after diagnosis, up from 49% in the late 1970s. Lung cancer five-year survival rose from 13% for those diagnosed between 1975 and 1979 to 29% between 2016 and 2022, while lymphoid leukaemia survival in children and adolescents up to 19 rose from 57% to 90%. Liver cancer survival has tripled to 22% since the mid-1990s, though gains remain uneven across malignancies.
An encapsulated cell-based "biologics factory" using an immunomodulatory alginate formulation sustained stable serum titers of the HIV-neutralizing mAb 3BNC117 for 1 year in immunocompetent mice, supported by an anti-inflammatory, proresolving immune niche that attenuates fibrosis. The platform produced 13 diverse mAbs from an allogeneic cell chassis, and in a nonhuman primate subcutaneous implant maintained stable ipilimumab titers for more than 6 months with no detectable toxicity, antidrug antibodies, or adverse events across a three-dose escalation. A retrievable macrodevice allows on-demand termination and dose-proportional tuning, pointing toward replacing frequent injections with single-administration therapy.
Why it matters: It shows a single implant can deliver monoclonal antibodies for months to a year, replacing repeated injections.
Cryo-EM structures of RNA-bound and RNA-free ZNFX1 reveal how a regulatory insertion auto-inhibits the helicase-associated ATPase by occluding the RNA-binding groove. ZNFX1 acts as a bi-catalytic E3 ubiquitin ligase through an RNF213-like RZ finger and a newly identified Miz-like domain, with ubiquitin chains enhancing E3 activity. Patient mutations show the helicase/ATPase, E3 ligase, and connecting zinc-finger stalk are all required for function, and polymer assembly drives trans-auto-ubiquitylation controlling ZNFX1 stability.
Why it matters: Defines the structural mechanism linking an innate-immunity RNA helicase to ubiquitin signaling and patient mutations.
Carboplatin plus paclitaxel (CarboTaxol) and cyclophosphamide act as immunological adjuvants that improve the efficacy of heterologous prime-boost viral vector vaccines and enhance antigen-specific CD8+ T cell responses, independently of tumor presence. CarboTaxol drives early, antigen-independent expansion of stem-like TCF1+CD8+ T cells, seen also in patients with different cancer types, and disrupting TCF1 abolishes this adjuvant effect. Adding PD-1 blockade further improves tumor control and survival, supporting clinical testing of the triple combination.
Why it matters: It gives a mechanism, TCF1+CD8+ T cells, for combining chemotherapy with cancer vaccines and PD-1 blockade.
The rapid, innate-like responses of tissue-intrinsic γδ T cells to tissue stress and carcinogenesis acutely depend on the γδ T cell receptor, contrary to reports that these responses are TCR-independent. The work shows that the immunosurveillance these cells mediate requires TCRγδ signalling, resolving uncertainty about whether tissue γδ T cells act through adaptive or innate mechanisms. Clinical deployment of these cells will evidently need environments supportive of TCRγδ signalling.
A synthetic acid-responsive membranolytic peptide, aMPC16-CA50, induces a distinct immunogenic membranolytic cell death in tumour cells, marked by time-lagged rupture from lysosomal to plasma membranes. The peptide activated an inflammatory transcriptional program in tumour cells, boosting class I MHC antigen presentation on dendritic cells and T cell activation, and strengthened the efficacy of immune checkpoint blockade therapy in mice, where systemic administration was well tolerated. It works by hierarchically responding to the falling pH of the tumour extracellular environment and lysosomes, spatiotemporally controlling membrane rupture.
Lymphoid structures with germinal-centre-like formations exist in skull bone marrow, harbouring follicular-helper-like T cells that promote B cell activation and humoral immunity through CD40L, IL-21 and IFNγ signalling. These adaptive immune cells surveil CNS-derived antigens and contribute to anti-tumour immune responses in mouse brain cancer models, identifying skull bone marrow as a site of CNS immunosurveillance.
A new murine model of sarcomatoid urothelial carcinoma, BBN966, closely mirrors the human disease: it lacks basal and luminal gene expression, shows the highest epithelial to mesenchymal transition upregulation, and has a higher proportion of M2 macrophage gene expression. In the largest PD-L1 IHC cohort to date, 20 of 38 (52.6%) human SUC had CPS > 50, and anti-PD1 significantly inhibited BBN966 tumor growth, supporting the model for testing new therapies.
PAK4 drives melanoma immune evasion by boosting exosome release through two mechanisms: phosphorylation of Annexin-A2 at Ser26, which promotes S100A10-ANXA2 heterotetramer formation and multivesicular body docking, and stabilization of synaptotagmin-1 by blocking Trim21-mediated degradation, enabling SNARE complex assembly. PAK4-driven exosomes enriched in PD-L1 reduce CD8+ T cell numbers and impair their function in mouse models, and pharmacological PAK4 inhibition in patient-derived xenografts attenuates tumor progression and lowers circulating exosomal PD-L1. The work supports combining PAK4 inhibitors with immune checkpoint blockade to overcome resistance.
Why it matters: It defines a mechanism linking PAK4 to PD-L1 exosome release and supports combining PAK4 inhibitors with checkpoint blockade.
Neoadjuvant immune checkpoint inhibitors, alone or in combination, outperformed neoadjuvant BRAF/MEK inhibitors for long-term survival in a pooled analysis of 1,038 melanoma patients with 3-year and 5-year data from the International Neoadjuvant Melanoma Consortium. Patients achieving major pathological responses had better long-term survival across treatment types. The results position pathological response as a key indicator of durable benefit from neoadjuvant therapy.
Why it matters: Five-year pooled survival data across neoadjuvant regimens guide regimen choice for resectable melanoma.
An interferon-stimulated gene program in neutrophils, detectable before tumors diverge in their response, predicts resistance to anti-PD1 therapy in preclinical triple-negative breast cancer models. Persistent neutrophil IFN signaling in blood and tumor tracked with treatment failure, while genetic disruption of type I or type II interferon signaling in neutrophils improved anti-PD1 efficacy and durable anti-tumor immune memory. The work positions IFN-responsive neutrophils as blood-based biomarkers and therapeutic targets.
Why it matters: Identifies an early, blood-accessible neutrophil IFN signature that predicts anti-PD1 resistance and can be targeted.