It is perhaps obvious to state that patients with inborn errors of immunity (IEI) are primarily susceptible to infections. However, recent research confirms another concerning risk – an increased vulnerability to cancer, particularly hematological malignancies.
This increased cancer risk stems from the fact that some genetic variants disrupt both immune function and critical pathways involved in DNA damage repair, cell cycle regulation, and immune surveillance.
Genetic and Molecular Insights into Cancer Predisposition
The genetic and cellular lesions associated with IEI not only impair immune function but also contribute to cancer risk by affecting tumor suppressor mechanisms and DNA repair. For example, variants in ATM impair DNA damage response (DDR), leading to an increased risk of malignancies like lymphomas and leukemia. Also, patients with much more frequent disorders, like Common Variable Immune Deficiency, are at an increased risk of developing hematological malignancies and solid tumors.
These insights underscore the need for in depth characterization of the disease and strict cancer surveillance in IEI patients, as it enables early identification of those at higher risk for cancer and early recognition of malignancy. Understanding genetic variants and pre-cancerous conditions allows for tailored monitoring strategies, offering the potential for early detection and intervention.
The Immunologist’s Role in Early Cancer Detection and Intervention
Immunologists play a crucial role in identifying at-risk IEI patients through genetic screening and regular cancer monitoring. By identifying cancer-predisposing variants or syndromes, immunologists can recommend personalized surveillance strategies, such as more frequent imaging or blood tests.
It is increasingly recognized that cancer can be the first manifestation of IEI, as malignancy can occur early in the course of disease. As these patients are primarily treated by oncologists, shared knowledge and collaboration with immunologists is crucial to screen patients and avoid delayed diagnosis. Effective screening models need to be developed to integrate cancer care and immunological work-up in selected patients.
In complex cases where inborn errors of immunity patients develop malignancies, or when cancer patients acquire secondary immunodeficiencies, immunologists must be actively involved not only in monitoring and management but also in the treatment process itself. Their expertise is vital in shaping therapeutic strategies, managing immune-related complications, and supporting immune reconstitution. Close, ongoing collaboration with haematologists and paediatric oncologists is essential to ensure that treatment decisions are fully informed by an immunological perspective. This multidisciplinary approach enhances the precision and safety of care. Regular screenings, early interventions, and the implementation of targeted therapies and vaccinations can significantly reduce cancer risk, especially for lymphoproliferative disorders and other haematological malignancies. Only through shared decision-making and integrated care can we offer the best possible outcomes for this uniquely vulnerable patient population.
A Focused Meeting to Address This
Join us in Vienna, 18-20 November 2025 for the ESID EHA SIOPE Focused Symposium, where immunologists, haematologists, and paediatric oncologists will come together to address the complex interplay between immunodeficiencies, cancer, and haematological conditions. The programme features sessions on genetic diagnostics, cancer-predisposing syndromes, early detection, and collaborative treatment strategies.
Attendees will gain the latest insights, exchange best practices, and strengthen multidisciplinary care pathways. For immunologists, they will be empowered not only to enhance prevention through early screening but also to play a central role in the treatment and co-management of malignancies in immunodeficient patients.
A Collaborative Path Forward in Cancer Prevention and Treatment
As the links between immunodeficiencies and malignancies become clearer, the field is entering a pivotal phase – moving beyond recognition into actionable, integrated care models. The challenge now is to translate our growing genetic and immunological understanding into standardized pathways for early detection, risk stratification, and shared treatment protocols. This next chapter will demand not only continued research, but also seamless collaboration across specialties to deliver truly personalised care.
The ESID EHA SIOPE Focused Symposium 2025 is where this momentum becomes strategy – uniting communities to shape the future of multidisciplinary care for these high-risk patient populations.