Harnessing immunotherapy for pediatric T-cell malignancies

Pediatric T-cell hematologic malignancies are a diverse group of rare cancers. The most common pediatric T-cell malignancies include T-cell acute lymphoblastic leukemia (T-ALL) and anaplastic large cell lymphoma (ALCL). Although the overall survival rates have improved markedly in recent years, children with relapsed T-ALL and ALCL have very low rates of cure and few salvage therapies exist. Current treatment regimens rely on toxic chemotherapies with significant short- and long-term morbidity. Immunotherapies, including antibodies and adoptive cellular therapies, have revolutionized the treatment of B-cell malignancies in pediatrics. The adaptation of these therapies to T-cell malignancies has been slower because of challenges implicit in the design and implementation of immunotherapies for T-cell malignancies, including the potential risks of fratricide, immunosuppression, and graft versus host disease (GVHD). We present a review of current challenges in the development of immunotherapies for T-cell hematologic malignancies, potential solutions and therapies under investigation. We include a particular focus on T-ALL and ALCL. Immunotherapies offer promising strategies to improve outcomes in children with T-cell malignancies, particularly in the setting of relapse. Optimizing efficacy, mitigating toxicity, and safely integrating with conventional therapies are key considerations as immunotherapies are translated into the clinic.