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Mismatch repair‐deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD‐L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve. All cases had high truncal mutation burdens. Despite pervasive ITH, driver aberrations showed a clear hierarchy. Those in WNT/β‐catenin, mitogen‐activated protein kinase, and TGF‐β receptor family genes were almost always truncal. Immune evasion (IE) drivers, such as inactivation of genes involved in antigen presentation or IFN‐γ signalling, were predominantly subclonal and showed parallel evolution. These IE drivers have been implicated in immune checkpoint inhibitor resistance or sensitivity. Clonality assessments are therefore important for the development of predictive immunotherapy biomarkers in MMRd CRCs. Phylogenetic analysis identified three distinct patterns of IE driver evolution: pan‐tumour evolution, subclonal evolution, and evolutionary stasis. These, but neither mutation burdens nor heterogeneity metrics, significantly correlated with T‐cell densities, which were used as a surrogate marker of tumour immunogenicity. Furthermore, this revealed that genetic and T‐cell infiltrates coevolve in MMRd CRCs. Low T‐cell densities in the subgroup without any known IE drivers may indicate an, as yet unknown, IE mechanism. PD‐L1 was expressed in the tumour microenvironment in most samples and correlated with T‐cell densities. However, PD‐L1 expression in cancer cells was independent of T‐cell densities but strongly associated with loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD‐L1 expression by cancer cells and may contribute to a higher recurrence risk of MMRd CRCs with impaired CDX2 expression. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Introduction Patients with gastrointestinal (GI) cancers have an increased risk of serious complications and death from SARS-CoV-2 infection. The immunogenicity of vaccines in patients with GI cancers receiving anti-cancer therapies is unclear. We conducted a prospective study to evaluate the prevalence of neutralizing antibodies in a cohort of GI cancer patients receiving chemotherapy following SARS-CoV-2 vaccination. Materials and Methods Between September 2020 and April 2021, patients with cancer undergoing chemotherapy were enrolled. At baseline (day 0), days 28, 56, and 84, we assessed serum antibodies to SARS-CoV-2 spike (anti-S) and anti-nucleocapsid (anti-NP) and concomitantly assessed virus neutralization using a pseudovirus neutralization assay. Patients received either the Pfizer/BioNTech BNT162b2, or the Oxford/AstraZeneca ChAdOx1 vaccine. Results All 152 patients enrolled had a prior diagnosis of cancer; colorectal (n = 80, 52.6%), oesophagogastric (n = 38, 25.0%), and hepato pancreatic biliary (n = 22, 12.5%). Nearly all were receiving systemic anti-cancer therapy (99.3%). Of the 51 patients who did not receive a vaccination prior to, or during the study, 5 patients had detectable anti-NP antibodies. Ninety-nine patients received at least one dose of vaccine prior to, or during the study. Within 19 days following the first dose of vaccine, 30.0% had anti-S detected in serum which increased to 70.2% at days 20-39. In the 19 days following a second dose, anti-S positivity was 84.2% (32/38). However, pseudovirus neutralization titers (pVNT80) decreased from days 20 to 39. Conclusion Despite the immunosuppressive effects of chemotherapy, 2 doses of SARS-CoV-2 vaccines are able to elicit a protective immune response in patients' ongoing treatment for gastrointestinal cancers. Decreases in pseudoviral neutralization were observed after 20-39 days, re-affirming the current recommendation for vaccine booster doses. Clinical Trial Registration Number NCT04427280. [ABSTRACT FROM AUTHOR]

Early diagnosis remains a major limitation of cancer outcomes with ethnicity and deprivation being determinants of inequalities that impact outcomes. Prostate cancer suffers from lower incidence rates and higher mortality rates in the most deprived versus the least deprived groups. We developed the 'Man Van' to enable high-risk male patients' from deprived communities and ethnic minorities increased access to health care to address these health inequalities. Between December 2021 and December 2022 the Man Van project was piloted in eight different locations chosen using geospatial targeting based on ethnic minority populations and deprivation scores. The primary outcome measures were the prevalence of prostate cancer and other health conditions. 810 men were recruited to be seen at our Man Van clinics with 610 men attending. 48% of attendees were non-White including 30% of men who were Black. 420 men had PSA tests performed with a median PSA of 1 μg/L. 15 prostate cancers were diagnosed (3.6%; 95% CI 2.0-5.9) with 10 of these being clinically significant disease. Black men were more likely to be diagnosed compared to white men: 7.1% versus 1.8% (p < .05). The Man Van project is a novel approach to tackling health inequalities combining awareness raising, improved access to healthcare as well as ease of follow-up. Comparatively high levels of prostate cancers were diagnosed at early stages and high levels of other health conditions were found which could improve the economic value of the service., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)