Volume 21 Issue 6, June 2021

Pfister et al. demonstrate a role for unconventionally activated CD8⁺PD1⁺ T cells in NASH-HCC, which limits response to immunotherapy.

Bertocchi et al. show that tumour-resident bacteria in colorectal cancer disseminate to the liver via an impaired gut vascular barrier and promote the liver pre-metastatic niche.

Tello-Lafoz et al. find that the increased rigidity of cancer cells during metastasis can result in a biophysical vulnerability to killing by cytotoxic lymphocytes through a form of mechanosurveillance.

Kaczanowska, Beury et al. find that the presence of a distant tumour induces immunosuppressive programmes in the lung, and that treatment of mice with genetically engineered myeloid cells expressing interleukin-12 reduces metastatic burden and improves survival.

An improved understanding of tumour immunology and therapy must assess the systemic immune landscape beyond the tumour microenvironment. This Review outlines peripheral immune cell reorganization in response to tumour growth and therapy, their contribution to immunotherapy responses and their potential as diagnostic or predictive biomarkers.

This Review broadly discusses therapeutic cancer vaccines, covering resistance mechanisms and strategies to overcome these, how to improve the antigen repertoire for vaccines and vaccine platforms, and approaches for enhancing immunotherapy efficacy.

This Review discusses the role of functional (impacting tumour phenotype) and non-functional intra-tumour heterogeneity (ITH) in cancer evolution, highlighting the importance of considering genetic and non-genetic factors and their impact on patient outcomes.

This Perspective highlights the evidence from basic and translational research that genetic sex influences multiple factors that can contribute to cancer development and treatment responses, and suggests that including genetic sex considerations in treatments for patients with cancer will improve outcomes.