A guide towards immunotherapeutic responsiveness in pediatric tumors: Assembling the intricate puzzle of the pediatric tumor immune landscape through synthesis of scRNA-sequencing analysis

Abstract

In the past decade, immunotherapy has revolutionized the field of cancer treatment. Although successful in certain cancer types, the overall clinical response of immunotherapies is inconsistent and varies significantly among cases. The clinical results of immunotherapy are especially disappointing in pediatric patients, as they fail to respond to standard immunotherapeutic agents relying on a preexisting adaptive antitumor immune response. Additionally, an extreme biological heterogeneity across pediatric cancer types and individual patients creates a unique immune TME for each individual patient, influencing immunotherapeutic treatment response. Distinct tumor immune profiles thus desire specific personalized immunotherapeutic approaches. An accurate characterization of the cellular and molecular components at play in the immune TME of distinct pediatric cancer subtypes is therefore crucial to develop tailored immunotherapeutic applications in pediatric oncology. In this research, we conducted a meta-analysis on studies analyzing the immune landscape of pediatric cancer types using single-cell RNA sequencing. The aim was to investigate the total immune cell infiltration in solid tumors and in hematologic malignancies. Subsequently, we focused on obtaining distinct immune cell subset fractions as part of the total immune cell population in solid tumors. We systemically searched the PubMed database using the combination of a specific set of search terms. Furthermore, we also briefly searched titles of citations within the acquired publications. This resulted in a total of 12 identified publications that passed eligibility criteria, which were to be used in our meta-analysis. The analysis and synthesis of our obtained data led to a comprehensive overview of the immune TME across pediatric solid cancers, thereby creating a pan-cancer immune atlas. This atlas is eventually ought to guide future immunotherapeutic responsiveness and immunotherapeutic strategy development for pediatric solid tumors. Given the absence of information on functional cell states in our atlas, the potential clinical utility of our pediatric immune atlas has to be taken with caution. Thus, our created pediatric immune atlas as presented in its current form, while valuable, should be interpreted with vigilance if used to directly guide immunotherapeutic decision-making. This meta-analysis should therefore be seen as a foundational step towards a broader understanding of the immunological character of TME’s across pediatric solid tumors.