Hallmarks and correlates of effective adoptive cell immunotherapy for cancer

Cancer immunotherapies have shown promise and success in a number of different types of tumours, yet many solid epithelial tumours remain recalcitrant. Somatic mutations in tumour cells can lead to the expression of neoantigens, which are potent targets of the human antitumour immune response. These can be targeted through adoptive cell transfer (ACT) of neoantigen-specific T cells, including tumour-infiltrating lymphocytes (TILs) or T cell receptor (TCR)-engineered T cells (TCR-T cells), an approach that has been shown to achieve tumour regression in patients with different types of metastatic solid tumours including melanoma, breast and gastrointestinal cancer. Immunogenomics, systems immunology and genome editing now provide multidisciplinary tools to design cell therapies against solid cancer. Here, we review historical efforts and our current conceptual understanding of ACT using TILs or TCR-T cells. Moreover, we highlight emerging correlates of response to ACT and novel strategies that integrate tumour immunology, cancer genomics, computational biology and T cell engineering for the development of next-generation cellular immunotherapies.