Protein Level Predicts Immunotherapy Response in Bowel Cancer: A Promising Breakthrough
In a significant advancement for the field of oncology, researchers at the Francis Crick Institute and Barts Cancer Institute, part of Queen Mary University of London, have unveiled findings that shed light on the predictive capabilities of a specific protein, CD74, in determining responses to immunotherapy among patients with bowel cancer. This research, published in the esteemed journal Cancer Cell, opens up exciting possibilities for improving treatment outcomes and broadening access to immunotherapy for previously ineligible patient groups.
Bowel cancer stands as the fourth most common cancer in the UK, and its impact as the second leading cause of cancer-related mortality cannot be overstated. The disease is classified into two main subtypes: deficient and proficient, distinguished by the presence or absence of proteins responsible for DNA repair mechanisms. Notably, while immunotherapy has shown transformative results in the treatment of the deficient subtype, it remains largely inaccessible for the proficient subtype, which encompasses around 90% of bowel cancer cases.
Immunotherapy drugs leverage the body’s immune system to combat cancerous cells, demonstrating remarkable efficacy in specific patient populations. However, the challenge lies in the fact that these drugs are effective in only approximately half of the patients with the deficient subtype, leaving a vast majority without viable treatment options. The inadequacy of immunotherapy for the proficient subtype raises essential questions: What are the underlying mechanisms that dictate the effectiveness of these treatments, and how can we expand their applicability to a broader patient base?
The research team undertook a comprehensive observational study to investigate the immune environment surrounding tumours and identify reliable indicators of immunotherapy success. By meticulously analyzing tissue samples from individuals with diverse subtypes and responses to treatment, the researchers aimed to unravel the complex interplay between immune cells and cancer cells. Their findings underscored the necessity of three distinct immune cell types—T cells, natural killer (NK) cells, and macrophages—being present in close proximity to cancer cells for an effective immunotherapeutic response.
Interestingly, the presence of these immune cells alone did not guarantee a positive outcome; the functionality of the immune environment was crucial. It was observed that T cells, when activated and present alongside macrophages, utilized specific signalling pathways to produce important molecules known as interferons. These interferons acted as messengers, orchestrating a robust immune response against tumour cells. The research illuminated that while higher signals were predominantly observed in responsive tumours of the deficient subtype, a surprising number of proficient subtype tumours exhibited comparable immune signalling, suggesting a potential for responsiveness that had previously gone unnoticed.
Delving deeper, the researchers employed cutting-edge spatial transcriptomics technology to explore the relationship between immune cells and the expression of CD74 in tumoural tissues. Their investigations delineated a clear trend: tumours demonstrating high levels of CD74 expression were more likely to respond favorably to immunotherapy. This pivotal discovery raised the question of whether CD74 could serve as a definitive clinical marker for predicting patient response to treatment, irrespective of the subtype classification.
In light of these findings, the researchers conducted analyses using samples from several international clinical trials involving patients with the proficient subtype. The results indicated a startling disparity; individuals who exhibited heightened levels of CD74 were significantly more likely to respond to immunotherapy compared to those with lower concentrations of this protein. This clear correlation posits CD74 not merely as a biomarker, but as a potential cornerstone for personalized treatment approaches in bowel cancer.
Francesca Ciccarelli, a leading figure in the study and Principal Group Leader at the Cancer Systems Biology Laboratory, emphasized the implications of their work. With a strong conviction that testing for CD74 could redefine eligibility for immunotherapy, Ciccarelli noted that such an advancement could broaden access to life-saving treatments for a substantial portion of bowel cancer patients. Importantly, this research could also facilitate the identification of individuals within the deficient subtype who are unlikely to benefit from immunotherapy, enabling more informed clinical decision-making and reducing the risk of side effects from ineffective treatments.
Kalum Clayton, a former postdoctoral researcher involved in the study, expressed his enthusiasm regarding the merging of innovative technologies with computational analysis to address pivotal clinical questions in oncology. His remarks resonate with a broader sentiment shared within the research community: the excitement that accompanies the prospect of translating scientific breakthroughs into tangible benefits for patients and their families.
As the research team prepares to collaborate with Cancer Research Horizons, the emphasis will be on translating these promising findings into a practical diagnostic test for clinical implementation. This includes investigating the underlying reasons behind the overexpression of CD74 in macrophages and tumour cells, as well as exploring the presence of CD74 as a marker in other cancer types. These inquiries could pave the way for a broader understanding of cancer immunology, with profound implications for future treatment strategies.
Anna Kinsella, the Science Engagement Manager at Cancer Research UK, articulated the importance of such studies in the continuum of cancer research. Kinsella’s statement reaffirmed the need for ongoing investigation into the biological intricacies of tumours, aiming ultimately to enhance the precision of treatments administered to patients. With a robust foundation established through this recent study, there exists a palpable hope for a future where understanding the biology of cancer becomes paramount in unlocking better prevention, detection, and treatment modalities.
The collaborative efforts of the research team, which included partnerships with institutions such as UCL, the University of Pisa, King’s College London, the Sarah Cannon Research Institute, and the Veneto Institute of Oncology, underscore the importance of multidisciplinary approaches in unraveling the complexities of cancer. As this research progresses towards clinical application, the desire to enhance patient outcomes remains a driving force, embodying the ultimate goal of biomedical research.
In conclusion, the discovery surrounding CD74 as a predictive marker for immunotherapy response in bowel cancer signifies a leap forward in precision oncology. By bridging the gap between laboratory research and clinical practice, this breakthrough holds the promise of extending the benefits of immunotherapy to a broader cohort of patients, thus transforming the landscape of bowel cancer treatment in the coming years.
Subject of Research: Bowel Cancer and Immunotherapy
Article Title: Protein Level Predicts Immunotherapy Response in Bowel Cancer
News Publication Date: 16-Jan-2025
Web References: DOI link
References: Acha-Sagredo, A., Andrei, P., & Clayton, K. et al. (2025). A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer. Cancer Cell.
Image Credits: Francis Crick Institute
Keywords: Cancer immunotherapy, Bowel cancer, CD74, Colorectal cancer, Immune response, Precision oncology, Tumour markers.
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