The European Society of Medical Oncology (ESMO) Annual Congress took place on 17th-21st October, showcasing the latest advances and insights from the global oncology community. As Europe’s largest oncology meeting, ESMO brings together thousands of researchers, clinicians, and industry leaders for an exchange of cutting-edge research and clinical innovation.
Members of the Department of Oncology were in Berlin to present their research, chair sessions, and network with collaborators from across Europe and beyond. Below are some of the highlights from our department’s contributions to ESMO 2025.
CMV Serostatus and Response to Immunotherapy in Melanoma
Gusztav Milotay, DPhil student in the Fairfax lab, investigates immunological responses to immune checkpoint blockade (ICB) in melanoma. He was awarded a poster prize at ESMO 2025 for his work looking at the relationship between cytomegalovirus (CMV) serostatus and response to ICB in melanoma.
In earlier work, the Fairfax group demonstrated that CMV seropositivity was associated with improved treatment outcomes and reduced side effects in patients with melanoma receiving single agent anti-PD-1 immunotherapy, but not combination ICB. At ESMO, Gusztav presented new insights into the mechanisms behind this effect. Using immuno-transcriptomic profiling, the team identified molecular signatures linking CMV status to clinical outcomes.
Notably, CMV-positive patients showed specific induction of a cytotoxic gene set that was independently predictive of improved overall survival across all metastatic melanoma patients. This gene set was particularly elevated in a population of effector cells that expand following checkpoint blockade and are maintained by CCL5 signalling. Conversely, CMV- patients showed reduced T-cell cytotoxicity coupled to increased Treg activation.
The findings highlight a crucial role for chronic viral infection in cancer immunotherapy response, positioning CMV serostatus as a novel peripheral biomarker for predicting ICB response.
Predicting immune-related hepatitis in melanoma
Martin Little, Clinical Research Training Fellow, focuses on cancer immunogenetics, particularly the involvement of the immune system in melanoma. At ESMO 2025, Dr Little presented findings on the predictive relationship between pre-treatment serum alanine transaminase (ALT) and the risk of immune-related hepatitis in patients undergoing treatment with immune checkpoint inhibitors for melanoma.
While highly efficacious, immune checkpoint blockade is associated with a substantial risk of immune-related adverse events (irAEs). Immune-related hepatitis, in particular, is a common cause of severe irAEs. Predicting an individual’s hepatitis risk prior to treatment initiation could guide treatment choices to maximise efficacy while minimising morbidity.
Using clinical, radiological, biochemical and haematological data, Dr Little explored potential predictive biomarkers of hepatitis risk. Results showed that elevated pre-treatment serum ALT was strongly associated with subsequent hepatitis, as were its associated environmental risk factors.
An investigation into shared genetic effects between irAEs revealed that patients with both hypothyroidism and hepatitis had much higher hypothyroidism risk scores than those with hypothyroidism alone, implicating certain pleiotropic autoimmune hypothyroidism risk alleles such as PTPN22. These data suggest that baseline liver inflammation may be a major source of hepatitis risk, and that knowledge of these baseline patient factors could support the development of risk-adapted immunotherapy strategies.
ICON8B: Quality of life impact of a dose-dense chemotherapy regimen in advanced ovarian cancer
Sarah Blagden, Professor of Experimental Oncology and Lead for the Oxford Cancer Trials Office, presented health-related quality of life data from ICON8B: a Phase III randomised trial comparing first-line weekly dose-dense chemotherapy plus bevacizumab to the standard three-weekly chemotherapy plus bevacizumab in patients with high-risk stage III-IV epithelial ovarian cancer.
Previously reported data demonstrated a clinically significant improvement in progression-free and overall survival in those treated with the dose-dense weekly treatment regimen. Weekly paclitaxel, in combination with three-weekly carboplatin plus bevacizumab, improved median overall survival by 10.2 months compared to the current standard of care regimen which gives all three drugs on a 3-weekly schedule. The trial team concluded that the dose-dense weekly treatment approach should now be considered a standard-of-care first-line treatment option in this group.
At ESMO 2025, Prof. Blagden presented data on the impact of the different regimens on quality of life. All participants completed questionnaires before, during and after chemotherapy completion. Global QOL improved significantly in both groups, with no overall difference across the total 66-week follow-up period. While neuropathy developed more gradually in the weekly treatment group, it tended to persist longer. Social function was also marginally worse during treatment in the weekly group, but this resolved by completion of bevacizumab treatment.
These results reinforce that dose-dense weekly chemotherapy is an effective approach in advanced ovarian cancer, though patients should be appropriately counselled on potential quality of life impacts.
Targeting the STING Pathway: First-in-Human Trial Results
Eileen Parkes, Associate Professor and Consultant Medical Oncologist, specialises in innate tumour immunology, and is an international expert on the cyclic GMP–AMP synthase (cGAS)-STING innate immune pathway. At ESMO 2025, Dr Parkes presented initial findings from a Phase I, first-in-human trial of novel STING agonist, BI 1703880.
STING (STimulator of INterferon Genes) has emerged as a promising therapeutic target in recent years due to its role in the antitumor immune response. It is the central molecule in the cGAS-STING pathway, which detects the presence of cytosolic DNA and triggers immune activation through the production of type I interferons (IFNs) and proinflammatory cytokines. Preclinical data has demonstrated that STING activation induces PD-L1 and HLA upregulation in tumour cells, suggesting synergistic potential with anti-PD-1 antibodies.
BI 1703880 is a novel, systemically administered second-generation STING agonist, shown preclinically to induce tumour shrinkage and durable antitumour immunity. The open-label, dose escalation trial utilised a lead-in design to evaluate intravenous BI 1703880 in combination with intravenous ezabenlimab, an anti-PD-1 antibody, in patients with advanced solid tumours refractory to or ineligible for conventional treatments.
The combination was well tolerated across all dose levels, with predominantly grade 1-2 adverse events. Grade 1-2 cytokine release syndrome occurred in 7% of patients and only one patient experienced a dose-limiting toxicity (grade 2 pneumonitis). The trial team noted promising early signs of immune activation, including upregulated interferon-stimulated genes, increased tumour HLA expression, and tumour-infiltrating lymphocyte recruitment. Objective responses and prolonged disease control were observed in some patients despite heavy pre-treatment.
The study is ongoing to establish the recommended dose for expansion.
Emerging Insights into Cancer Immunotherapy
Ben Fairfax, Professor of Cancer Immunogenetics and Consultant in Medical Oncology, leads a lab focused on genetic and epigenetic determinants of inter-individual variation in immune responses, particularly in the context of melanoma. At ESMO 2025 Prof. Fairfax was an invited discussant in the proffered paper session, which highlighted key basic science discoveries shaping oncology practice.
He discussed two high-impact papers. The first, entitled ‘Parity and lactation induce T cell mediated breast cancer protection’ linked the known protective effects of pregnancy and breast feeding to the induction of resident memory CD8 T cells. The research team, led by Sherene Loi of the University of Melbourne, showed that pregnancy and lactation in murine models drove the accumulation of CD8+ T cells in the mammary gland and led to reduced tumour growth and increased tumour immune infiltration. These effects were abrogated by CD8⁺ T cell depletion.
Additionally, when looking at a cohort of around 1000 women with early-stage breast cancer, gene expression-derived immune infiltrate scores showed that parous women had significantly higher tumoural immune content, compared to nulliparous women.
Prof. Fairfax noted that key questions remain around the mechanisms driving this immune response, including what triggers CD8⁺ T cell residency, and how these insights might be leveraged clinically.
Prof. Fairfax also discussed new findings from Steven Lin at the University of Texas MD Anderson Cancer Center, demonstrating that SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade (ICB). In preclinical models, vaccination led to a substantial increase in type I interferon, triggering an innate immune response that primed CD8+ T cells against the tumour. Retrospective clinical analyses revealed that vaccination within 100 days of ICB treatment was associated with significantly improved median and three-year overall survival in multiple large cohorts.
These results demonstrate that mRNA vaccines targeting non-tumour-related antigens are potent immune modulators. In his talk, Prof. Fairfax noted that this has important implications for cancer vaccine trials: “It suggests that you need to use control random RNAs in the control arm as the vaccine might be having effects without needing to be designed to target neoantigens."