Revolutionizing Cancer Survival: How Immune Cell Levels in Blood Might Change teh Future of Diagnosis and Treatment

A new study published in Nature Genetics reveals a significant correlation between the number of immune cells in the blood of cancer patients and their survival rates. Researchers at UCL and the Francis Crick Institute developed Immune Lymphocyte Estimation from Nucleotide Sequencing (ImmuneLENS), a tool analyzing whole genome sequencing (WGS) data to determine the proportion of T cells and B cells—key components of the immune system—for the first time. This revelation offers a potential paradigm shift in cancer diagnosis and treatment.

Whole genome sequencing, using a simple blood sample, provides a complete map of an individual’s DNA. This detailed genetic blueprint allows scientists to assess immune cell counts, identify genetic alterations, and understand the body’s response to disease. The research team used ImmuneLENS to analyze over 90,000 WGS samples from the 100,000 Genomes Project, a collaborative effort between Genomics England and NHS England, including both healthy individuals and cancer patients.

The analysis revealed a lower proportion of circulating T cells in cancer patients compared to healthy individuals. Remarkably,the proportion of T cells proved a powerful predictor of cancer outcomes. Patients with higher T cell proportions experienced a 47% reduction in deaths within five years post-surgery—a statistically significant finding holding true across various cancer types, even when accounting for age and cancer stage.

Most immune system analysis until now has focused on the tumour itself, so the results we’re seeing using this new technique – which examines the number of immune cells in a person’s blood – are of considerable interest. what’s going on with immune cells in the blood seems to have a huge impact on cancer survival and might possibly be able to predict how long a cancer patient will survive better than the number of T cells in the tumour alone. There have been hints in previous research that this might be significant, but being able to analyze immune system data at this scale is game changing. The ability to compare immune cell changes in the blood and to what’s happening in the tumour habitat opens up new avenues for cancer research, and also healthcare research more widely. In terms of patient diagnosis and treatment, knowing whether a patient has relatively high or low numbers of immune cells in the blood, and how this corresponds to their prognosis, could help clinicians to decide on the best course of treatment for the individual.

Professor Nicholas McGranahan, senior author of the study, UCL Cancer Institute

Cancer arises from genetic mutations within cells, with specific mutations linked to particular cancer types. While immune cells typically identify and eliminate these risky mutations, cancer often evades this immune response and disrupts the immune system itself. Thus, assessing changes in both the local immune environment around the tumor and the broader immune system is crucial for understanding cancer progress and predicting treatment response.

The 100,000 Genomes Project, with its vast whole genome data from over 90,000 NHS patients, has provided researchers with an unprecedented view of genetic changes in both healthy and cancerous cells. However, until now, a comprehensive understanding of immune cell composition within both the tumor and the wider immune system has remained elusive. ImmuneLENS builds upon a 2021 method that calculated T cell proportions in whole exome sequencing data, considerably advancing this crucial area of research.

The study also revealed that the proportion of immune cells in the blood decreases with age in healthy individuals, but this decline occurs more rapidly in cancer patients. This affect was more pronounced in men than women, although the reasons for this sex-based difference and its impact on cancer survival remain unclear. Interestingly, individuals who appeared healthy at the time of sample collection but later developed cancer exhibited below-average B cell levels in their blood. This finding suggests potential early indicators of disease or pre-cancerous immune system changes that could warrant further inquiry.

Lots of approaches that measure immune cells from genetic data are like looking for a needle in a haystack. Our approach in this study rather looks at the haystack itself and asks how the presence of immune cells changes its overall shape. It’s a different, more efficient way of finding the needle. This new method, explained Dr. Robert Bentham, first author of the study from UCL Cancer Institute, allows for the creation of ample immune datasets from existing large-scale WGS cohorts, opening doors to explore immune system dynamics in health and disease across various medical fields.

ImmuneLENS also distinguishes between different types of B cells. As B cells mature, they specialize in producing specific antibodies to neutralize harmful substances. The study identified that B cells producing IgM/D antibodies (produced upon initial encounter with a foreign antigen) were the only type associated with improved cancer survival,highlighting their potential role in anti-tumor immunity and as a new biological marker for cancer diagnosis.

The researchers plan to integrate these biological markers into clinical practice, possibly adding them to existing cancer patient tests at no extra cost. A Cancer Research UK Biomarker Project Award will support this clinical translation. This is particularly relevant for predicting responses to immunotherapy, as the proportion of T cells in a tumor—a known biomarker—cannot be measured using current standard genomic tests.

Cancer Research UK is pleased to support this ongoing work investigating whether measuring immune cell levels in our blood can help predict cancer survival. We’re living in a golden age of research where we can use patient data in sophisticated ways to help us better understand cancer and how to beat it. Further research is needed, but this could one day become a tool to help doctors personalize treatment for people with cancer. Dr. Nisharnthi Duggan, Research Information Manager at Cancer Research UK, emphasized the potential impact of this research.

This research, part of the Cancer Research UK-funded TRACERx project, was made possible by access to data from the 100,000 Genomes Project, managed by genomics England. The findings represent a significant advancement in cancer research, offering hope for improved diagnosis, treatment, and ultimately, survival rates for cancer patients.