Personalized cancer immunotherapy: Immune biomarkers and combination immunotherapy

Cancer immunotherapies utilizing tumor-specific T-cell responses, immune-checkpoint blockade, and T-cell-based adoptive cell therapy, have recently shown durable responses in advanced patients with various cancers. However, there are still cancer types and patients who do not respond to these immunotherapies. Pretreatment immune status varies in cancer patients, and it correlates with prognosis after various cancer therapies including immunotherapy. The differential T-cell response is defined by positive (e.g., number of immunogenic mutated peptides derived from mainly passenger DNA mutations in cancer cells, polymorphisms of immune-related genes of patients) and negative (e.g., oncogene activation including driver DNA mutations) immune pathways along with environmental factors (e.g., intestinal microbiota, diet, smoking, infection history). These factors could be biomarkers for selection of the patients who are likely to respond to immunotherapy and furthermore could be therapeutic targets to improve efficacy of immunotherapy possibly by combination immunotherapy with interventions on multiple key regulation points in the antitumor T-cell responses. Personalized combination immunotherapy based on the evaluation of T-cell immune status is a promising strategy for cancer treatment.