Editorial: The promise of immunogenetics for precision oncology

disorders, shedding light on the mechanisms that drive malignant transformation and disease progression. In parallel, immunogenetics also offers valuable insights into the interactions occurring within the tumor microenvironment and the intricate communication between bystander immune cells and tumor cells. This, in turn, establishes the basis for patient-speci ﬁ c immunotherapeutic interventions


Editorial on the Research Topic
The promise of immunogenetics for precision oncology The concept of precision medicine (PM) was introduced as early as the times of Hippocrates and later emphasized by Sir William Osler, both fostering the perception that "It is much more important to know what sort of patient has a disease than what sort of disease a patient has". In the last 20 years, rapid advances in diagnostic technologies along with the development of novel targeted therapies have paved the way for the implementation of PM approaches in cancer treatment and prevention, based on the individual's tumor characteristics, such as the genomic profile and the composition of the microenvironment of the malignant cells (1).
In the context of hematological malignancies, the distinctive features of the patients' immune repertoires, namely the unique B-cell receptor (BcR) and/or T-cell receptor (TR) genetic rearrangements within their adaptive immune system, have evolved as highly promising tools for PM in patient stratification and disease monitoring. In the clinical setting, immunogenetics is the basis for clonality assessment which allows to chartacterize at the molecular level the architecture of a lymphoproliferation (2, 3). Additionally, immunogenetics has been proposed as a means of reliably assessing measurable residual disease (MRD) (4). Turning to translational research, immunogenetic analysis of immune repertoires has shed light on the complex biological heterogeneity of lymphoid malignancies, which is reflected in the observed clinical variability in everyday practice. Furthermore, accumulating evidence on intraclonal diversification of the immunoglobulin genes has further enhanced our understanding of the mechanisms driving disease ontogeny (5).
In this Research Topic of Frontiers in Oncology, a collection of ten papers provides different perspectives on the promise of immunogenetics in hemato-oncology, highlighting on the one hand the contribution of immunogenetics to the deeper and more precise understanding of the   Applications of immunogenetics for precision hemato-oncology. High-throughput studies on the features and dynamics of antigen receptor gene repertoires contribute to a refined understanding of the natural history of lymphoproliferative disorders, shedding light on the mechanisms that drive malignant transformation and disease progression. In parallel, immunogenetics also offers valuable insights into the interactions occurring within the tumor microenvironment and the intricate communication between bystander immune cells and tumor cells. This, in turn, establishes the basis for patient-specific immunotherapeutic interventions.
While these manuscripts underline the huge potential of immunogenetics to transform patient management and cancer treatment, it is important to also acknowledge the limitations of the available techniques. Although NGS-based approaches offer great analytical depth, immunogenetic analyses typically rely on a single biopsy or a small sample, which may not fully capture the entire tumor's complexity. To overcome this pitfall, high-resolution mapping at the single-cell level has been proposed as the upcoming breakthrough strategy, enabling the identification of novel biomarkers for disease monitoring and response to treatment. In this Research Topic, a review article focusing on the employment of single-cell technologies in CLL by Oder et al. describes in detail the current status of single-cell transcriptomics, genomics, epigenomics, immunogenetics and profiling of cellular subpopulations, of both malignant and non-malignant cells within the tumor microenvironment. Single-cell sequencing technology has already shown its potential in dissecting the complex landscape of CLL, with similar applications in other immune-mediated malignancies, however, as highlighted by the authors, several challenges still exist that must be addressed through an integrated multi-omics approach.
In summary, the articles in this Research Topic illustrate the vital role of immunogenetics in precision hemato-oncology by providing insights into the tumor's intratumor heterogeneity and immunogenicity; the interaction between the tumor and immune system; and, potential targets for immunotherapies. By harnessing this knowledge, researchers and clinicians are entering a new era with more tailored and effective stratification and treatment schemes for patients with cancer.