Combining immunotherapy and targeted therapies in cancer treatment

Abstract

The so-called targeted therapies and cancer immunotherapies are two novel treatment modalities that have recently begun to enter the oncology clinic. Targeted therapies and immunotherapy offer a number of possible synergies in treatment when used together; however, these combinations have not been well studied. Many targeted therapies against tumours affect pathways that are also crucial for immune development and function, which suggests the possibility that targeted therapies may help to optimize anti-tumour immune responses from immunotherapies. Similarly, immunotherapies may serve to consolidate impressive clinical responses from targeted therapies into long-lasting clinical remissions. Targeted therapies promote effective dendritic cell (DC) maturation, T cell priming, activation and differentiation into long-lived memory T cells, which suggests possible combinations of cancer vaccines along with targeted therapies to bolster vaccine responses, as well as effector T cell function. Targeted therapies may sensitize tumour cells to immune-mediated killing by increasing the expression of death receptors or 'distress' ligands while simultaneously diminishing the expression of pro-survival signals, which increases the efficiency of immune-mediated tumour clearance once immune cells are activated in vivo. Targeted therapies might diminish tumour-mediated immunosuppression by abrogating the production of tumorigenic inflammation and by inhibiting immunosuppressive cell types. Impairing immunosuppression improves effector T cell function and increases immune destruction of tumour targets, suggesting possible synergy with immunotherapies that are designed to generate anti-tumour T cells or to bolster their effector function. Important considerations regarding optimizing dose, sequence and timing of targeted therapies will be required when rationally designing future clinical trials in order to maximize anti-tumour efficacy while minimizing any immunosuppressive side effects.