Breakthrough Liver Cancer Immunology Research Published in Science Advances
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Professor Salim Khakoo, a renowned hepatologist, has recently published groundbreaking research on cancer immunology in Science Advances, a prestigious peer-reviewed journal.
Salim’s research , conducted at the University of Southampton —an institution with a strong history in immunotherapy research—offers promising new insights that could improve cancer treatment outcomes. This research was supported by Cancer Research UK , the Medical Research Council and Professors Anthony Purcell and Ralf Schittenhelm at Monash University Australia .
Salim’s work focuses on liver cancer, the fastest-growing cancer in the UK, both in terms of prevalence and mortality rates. Despite existing treatments, liver cancer remains a formidable challenge with a median survival rate of only 18 months to two years, significantly lower than many other cancers.
The Role of Killer Cells
A key aspect of Salim’s work is the study of ‘killer cells,’ crucial components of the immune system that constantly monitor and destroy emerging cancer cells. Their ability to specifically target and destroy cancer cells makes them a promising avenue for effective cancer treatments.
Previously, it was believed that these killer cells attacked cancer cells in a random manner. However, as Salim explains: “Our research challenges this notion. We have revealed a new mechanism by which the immune system recognises and targets cancer cells.”
The Role of Exportin 1 (XPO1)
Central to this research is the protein Exportin 1 (XPO1), which acts as a transport service within cells, moving important proteins from the nucleus – the cell's control centre – to the cytoplasm, the main body of the cell. In many cancers, XPO1 becomes overactive, exporting too many proteins, including tumour suppressors. These suppressors act as security guards, preventing uncontrolled cell growth. When XPO1 removes them from the nucleus, it disables their protective function, allowing cancer cells to multiply unchecked.
Salim explains: “Our research shows that cells containing high levels of the protein XPO1 are specifically targeted by ‘killer cells.’ XPO1 is therefore a critical marker that helps killer cells recognise and attack cancer cells.”
Using The Cancer Genome Atlas
To strengthen these findings, Salim used data from The Cancer Genome Atlas (TCGA), a comprehensive project studying the genetic makeup of over 30 types of cancer. TCGA's vast dataset allowed Salim to identify patterns and common genetic changes across different cancers.
“The impact of this research extends beyond just liver cancer,” Salim notes. “By analysing this data, we demonstrated that patients with both active ‘killer cells’ and high levels of XPO1 had significantly better survival rates. This holds true for a range of cancers—not just liver cancer—including head and neck cancers, endometrial cancers, bladder cancer, and breast cancer.”
Clinical Implications and Future Research
Salim’s findings therefore demonstrates a new relationship between killer cells and XPO1, where killer cells effectively target more malignant cancer cells and this improves survival in liver and other cancers. This discovery has profound clinical relevance, leading to personalised medicine approaches for hard-to-treat cancers.
Salim’s ongoing research is currently developing new treatments based on these insights and supported by grants from CRUK Horizons and Innovate UK through the spin-out company Kargenera, offering hope for improved patient outcomes across multiple cancer types.