Graft-Versus-Solid-Tumor Effect: From Hematopoietic Stem Cell Transplantation to Adoptive Cell Therapies

Abstract

Abstract After allogeneic hematopoietic stem cell transplantation (HSCT), donor lymphocytes may contribute to the regression of hematological malignancies and select solid tumors, a phenomenon referred to as the graft-versus-tumor effect (GVT). However, this immunologic reaction is frequently limited by either poor specificity resulting in graft-versus-host disease or the frequency of tumor-specific T cells being too low to induce a complete and sustained anti-tumor response. Over the past 2 decades, it has become clear that the driver of GVT following allogeneic HSCT is T-cell-mediated recognition of antigens presented on tumor cells. With that regard, even though the excitement for using HSCT in solid tumors has declined, clinical trials of HSCT in solid tumors provided proof of concept and valuable insights leading to the discovery of tumor antigens and the development of targeted adoptive cell therapies for cancer. In this article, we review the results of clinical trials of allogeneic HSCT in solid tumors. We focus on lessons learned from correlative studies of these trials that hold the potential for the creation of tumor-specific immunotherapies with greater efficacy and safety for the treatment of malignancies.