Advances in single-cell multi-omics technologies have deepened our understanding of cancer biology by integrating genomic, transcriptomic, epigenomic, and proteomic data at single-cell resolution. These single-cell multi-omics technologies provide unprecedented insights into tumour heterogeneity, tumour microenvironment, and mechanisms of therapeutic resistance, enabling the development of precision medicine strategies. The emerging field of single-cell multi-omics in genomic medicine has improved patient outcomes. However, most clinical applications still depend on bulk genomic approaches, which fail to directly capture the genomic variations driving cellular heterogeneity. In this review, we explore the common single-cell multi-omics platforms and discuss key analytical steps for data integration. Furthermore, we highlight emerging knowledge in therapeutic resistance and immune evasion, and the potential of new therapeutic innovations informed by single-cell multi-omics. Finally, we discuss the future directions of the application of single-cell multi-omics technologies. By bridging the gap between technological advancements and clinical implementation, this review provides a roadmap for leveraging single-cell multi-omics to improve cancer treatment and patient outcomes.

Melanoma is the leading cause of global skin cancer-related death and currently ranks as the third most commonly diagnosed cancer in Australia. Melanoma patients with in-transit metastases (ITM), a type of locoregional metastasis located close to the primary tumor site, exhibit a high likelihood of further disease progression and poor survival outcomes. Immunotherapies, particularly immune checkpoint inhibitors (ICI), have demonstrated remarkable efficacy in ITM patients with reduced occurrence of further metastases and prolonged survival. The major challenge of immunotherapeutic efficacy lies in the limited understanding of melanoma and ITM biology, hindering our ability to identify patients who likely respond to ICIs effectively. In this review, we provided an overview of melanoma and ITM disease. We outlined the key ICI therapies and the critical immune features associated with therapy response or resistance. Lastly, we dissected the underlying biological components, including the cellular compositions and their communication networks within the tumor compartment, to enhance our understanding of the interactions between immunotherapy and melanoma, providing insights for future investigation and the development of drug targets and predictive biomarkers.

Recent advances in single-cell transcriptomics have greatly improved knowledge of complex transcriptional programs, rapidly expanding our knowledge of cellular phenotypes and functions within the tumour microenvironment and immune system. Several new single-cell technologies have been developed over recent years that have enabled expanded understanding of the mechanistic cells and biological pathways targeted by immunotherapies such as immune checkpoint inhibitors, which are now routinely used in patient management with high-risk early-stage or advanced melanoma. These technologies have method-specific strengths, weaknesses and capabilities which need to be considered when utilising them to answer translational research questions. Here, we provide guidance for the implementation of single-cell transcriptomic analysis platforms by reviewing the currently available experimental and analysis workflows. We then highlight the use of these technologies to dissect the tumour microenvironment in the context of cancer patients treated with immunotherapy. The strategic use of single-cell analytics in clinical settings are discussed and potential future opportunities are explored with a focus on their use to rationalise the design of novel immunotherapeutic drug therapies that will ultimately lead to improved cancer patient outcomes.

Melanoma is known as one of the most immunogenic tumours and is often characterised by high mutation burden, neoantigen load and immune infiltrate. The application of immunotherapies has led to impressive improvements in the clinical outcomes of advanced stage melanoma patients. The standard of care immunotherapies leverage the host immunological influence on tumour cells, which entail complex interactions among the tumour, stroma, and immune cells at the tumour microenvironmental level. However, not all cancer patients can achieve a long-term durable response to immunotherapy, and a significant proportion of patients develops resistance and still die from their disease. Owing to the multi-faceted problems of tumour and microenvironmental heterogeneity, identifying the key factors underlying tumour progression and immunotherapy resistance poses a great challenge. In this review, we outline the main challenges to current cancer immunotherapy research posed by tumour heterogeneity and microenvironment complexities including genomic and transcriptomic variability, selective outgrowth of tumour subpopulations, spatial and temporal tumour heterogeneity and the dynamic state of host immunity and microenvironment orchestration. We also highlight the opportunities to dissect tumour heterogeneity using single-cell sequencing and spatial platforms. Integrative analyses of large-scale datasets will enable in-depth exploration of biological questions, which facilitates the clinical application of translational research.

Untreated chronic hepatitis B virus (HBV) infection can lead to chronic liver disease and may progress to cirrhosis or hepatocellular carcinoma (HCC). HBV infection has been prevalent in Vietnam, but there is little information available on the genotypes, sub-genotypes, and mutations of HBV in patients with HBV-related HCC confirmed by histopathological diagnosis. We studied the molecular characteristics of HBV and its genetic variants in Vietnamese HCC patients after liver tumor resection. We conducted a descriptive cross-sectional study on 107 HBV-related HCC hospitalized patients from October 2018 to April 2019. The specimens collected included EDTA anticoagulant blood and liver tissues. Extracted HBV DNA was subjected to whole genome sequencing by the Sanger method. We discovered 62 individuals (57.9%) with genotype B and 45 patients (42.1%) with genotype C, with only sub-genotypes B4 and C1. Among the mutations, the double mutation, A1762T-G1764A, had the most significant frequency (73/107 samples; 68.2%) and was higher in genotype C than in genotype B (p < 0.001). The most common genotypes found in HCC patients in this investigation were B and C, with sub-genotypes B4 and C1 for each. The prevalence of genotype B4 was greater in HBV-infected Vietnamese HCC patients.

Background: Primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri is a rare and devastating infection of the central nervous system, often diagnosed late, due to its rapid progression and nonspecific symptoms. Case Presentation: We report one of the youngest documented pediatric Vietnamese cases of PAM in a 10-month-old girl from the Mekong Delta, Vietnam. The diagnosis was confirmed through multiplex real-time PCR (MPL-rPCR), microscopy, and sequencing. Clinical data were gathered retrospectively from medical records, and additional details were provided by the patient’s family. Treatment regimens, disease progression, and diagnostic challenges were reviewed and compared to existing literature. With intensive treatment, the child survived for 14 days, representing one of the longest reported pediatric PAM survival durations. No direct exposure to untreated freshwater or other typical risk factors for Naegleria fowleri infection was identified, underscoring the unique epidemiological nature of this case. MPL-rPCR enabled timely detection of the pathogen and demonstrated its utility in resource-limited settings. Conclusions: This case highlights the critical need for rapid, accessible diagnostic tools such as MPL-rPCR, particularly in resource-constrained environments where traditional diagnostics may not be feasible. It also emphasizes the importance of international collaboration and investment in cost-effective diagnostics and novel therapeutic strategies. The geographical expansion of PAM due to climate change further underscores the urgency of these measures to improve health outcomes in vulnerable populations.