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Pancreatic ductal adenocarcinoma carries a poor prognosis, with pancreatectomy as the only potentially curative option. This Phase II trial assessed distant metastasis-free survival in locally advanced disease using GVAX vaccine, pembrolizumab, and SBRT following chemotherapy.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

Four leading tumour immunologists provide their opinions on the determinants of immunogenicity and how we might therapeutically improve tumour immunogenicity in the future.

The aging immune system is characterized by changes in immune cell frequencies and functionality. Here the authors report dynamics of age-related divergence of circulating immune responses in patients with solid tumors treated with immune checkpoint inhibitors

In this phase 1 trial, treatment of patients with fibrolamellar hepatocellular carcinoma with a therapeutic peptide vaccine targeting the fusion kinase DNAJB1–PRKACA, which is the driver of the disease, together with nivolumab and ipilimumab, was safe and led to encouraging preliminary clinical responses, and translational analysis showed activation of immune responses.

Cancer research in recent years has been marked by significant developments in understanding disease biology and foundational discoveries that have changed clinical practice. Ten cancer researchers take stock of the field, the advances that excite them, key outstanding questions and breakthroughs they anticipate looking forward.

Roussos-Torres and colleagues perform a phase Ib clinical trial of entinostat, nivolumab and ipilimumab in individuals with advanced HER2-negative breast cancer, report on safety and response and characterize the immune-modulatory effects.

GM-CSF-secreting whole-cell cancer vaccine (GVAX) promotes T-cell response against a range of tumor associated antigens in patients with pancreatic adenocarcinoma (PDA). Here the authors report the results of the initial three treatment arms of a platform trial of neoadjuvant and adjuvant GVAX alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable PDA.

Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.

Cancer prevention vaccines have reduced cancer-related mortalities, yet therapeutic cancer vaccine development and clinical translation continues to face challenges. Here, Zaidi, Jaffee and Yarchoan summarize the failures of cancer vaccines of the past, to highlight recent advancements in the field.

Responses to immune checkpoint inhibitors in patients with pancreatic ductal adenocarcinoma (PDA) remain low and alternative combinatorial approaches are warranted. Here the authors report the results of a phase 2 clinical trial of entinostat (histone deacetylases inhibitor) and nivolumab (anti-PD-1 inhibitor) in patients with metastatic PDA.

Here the authors functionally characterize hepatocellular carcinoma associated tertiary lymphoid structures (TLS) in patients treated with neoadjuvant immunotherapy and present further evidence for using these TLS as a biomarker of response to therapy.

Treatment of patients with advanced hepatocellular carcinoma with a personalized DNA vaccine in combination with anti-PD-1 therapy was safe and led to encouraging clinical efficacy, with immunological analyses confirming the induction of tumor antigen-specific T cell responses.

Clinical trials reveal that personalized vaccines can boost immune-cell responses to brain tumours that don’t usually respond to immunotherapy. The findings also point to how to improve such treatments.

Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.

Retinal vascular disease treatments involve frequent pharmacological intraocular administrations. Here the authors present a method to increase the half-life of injected drugs by fusing these to a hyaluronan-binding peptide, which might lead to less frequent retinal disease treatments.

Substantial nitrogen fixation at sub-nanomolar molybdenum concentrations without alternative nitrogenases, with important implications for early Earth primary productivity, according to results from a ferruginous, low-sulfate, low-Mo, cyanobacteria-dominated lake.

Predicting clinical outcomes in cancer using neoantigen burden is imperfect because current algorithms use only the binding affinity of putative neoantigens to HLA. A new study models pancreatic tumour response through a deeper understanding of tumour immunology, providing new tools for identifying neoantigens and characteristics that define their quality.

Enterotoxigenic Bacteroides fragilis, a bacterium from the intestinal flora, may promote colon tumor formation through a pathway that involves Stat3 expression and T helper type 17 immune responses.

In this Review, Yarchoanet al. discuss the potential of targeting tumour-specific antigens (neoantigens) to increase antitumour immunity and present a framework for personalized cancer immunotherapy based on the identification and specific targeting of individual tumour neoantigens.

In this Roadmap, Furth, Sethupathy and colleagues discuss advances in our understanding of the mechanisms and treatments of fibrolamellar carcinoma, a rare hepatic cancer that primarily occurs in adolescents and young adults. Recommendations for future progress in research and clinical trials are proposed.

Important research efforts are being made to develop therapeutic strategies targeting the tumour microenvironment in pancreatic adenocarcinoma. The authors of this Review describe the apparent contradiction between preclinical studies and clinical outcomes observed to date, presenting more sophisticated strategies under active investigation.

This protocol describes procedures for learning cellular and molecular processes from single-cell RNA-sequencing data using the non-negative matrix factorization algorithm Coordinated Gene Activity across Pattern Subsets. Parallel analysis is demonstrated in Python, R and GenePattern Notebook.