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.
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.
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.
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.
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.
Yuan et al. described in Nature an acid-responsive membranolytic peptide that separates lysosomal rupture from later plasma membrane rupture, turning oncolysis into immunogenic cell death. The design allows systemic administration, induces antigen-specific immunity and sensitizes tumors to programmed death ligand 1 blockade with limited toxicity.
Why it matters: A preclinical Nature study shows an oncolytic peptide design that sensitizes tumors to PD-L1 blockade.
Desharnais et al. show in Nature that across diverse mouse models, anti-PD-1 sensitivity tracks more closely with the diet-microbiome-metabolite ecosystem than with obesity-associated metabolic dysfunction. The findings point to body mass index as an incomplete proxy for host biology and suggest strategies to improve anti-PD-1 efficacy without inducing obesity.
Why it matters: Reframes BMI as an incomplete predictor of anti-PD-1 response, with implications for immunotherapy stratification.
A systematic review and meta-analysis of 15 randomized trials with 7947 patients found that adding immune checkpoint inhibitors to radiotherapy improved overall survival (HR 0.865) and progression-free survival (HR 0.799) across cancers, with the clearest gains in non-small-cell lung cancer and cervical cancer. Adjuvant ICI timing showed stronger benefit (OS HR 0.742; PFS HR 0.638), but grade 3 or higher treatment-related and immune-related adverse events were more frequent (OR 1.227 and 2.217).
Mallard de La Varende et al. show that dysbiosis-associated tauro-conjugated bile acids drive non-response to immune checkpoint inhibition therapy in cancer, offering a mechanism for why antibiotics compromise ICI efficacy. The study, published in Cancer Cell, also identifies γ-glutamyl transferase (γGT) as a predictive biomarker for ICI response.
Hernández-Verdin et al. show that cancer-derived gamma-aminobutyric acid (GABA) acts as an immunosuppressant factor that renders tertiary lymphoid structures (TLSs) dysfunctional and drives resistance to immunotherapy in some tumors. Targeting GABA together with immunotherapy reshaped the tumor and TLS microenvironment and improved therapeutic efficacy. The work points to GABA as a candidate target for overcoming TLS-associated immunotherapy resistance.
Why it matters: Identifies a mechanism of immunotherapy resistance and a targetable candidate, GABA, in TLS biology.