Augmenting the synergies of chemotherapy and immunotherapy through drug delivery

Despite the recent approvals of multiple cancer immunotherapies, low tumor immunogenicity and immunosuppressive tumor microenvironments prevent a large portion of patients from responding to these treatment modalities. Given the immunomodulatory and adjuvant effects of conventional chemotherapy as well as its widespread clinical use, the use of chemotherapy in combination with immunotherapy (so-called chemoimmunotherapy) is an attractive approach to potentiate the effects of immunotherapy in more patient populations. However, due to the limited extent of tumor accumulation, poorly controlled interactions with the immune system, and effects on systemic healthy tissues by chemotherapeutic drugs, the incorporation of anti-cancer agents into biomaterial-based structures, such as nanocarriers, is highly attractive to improve the safety and efficacy of chemoimmunotherapy. Herein, we review the recent progress in drug delivery systems (DDSs) for potentiating the immunomodulatory effects of chemotherapeutics in chemoimmunotherapy, which represent among the most promising next generation strategies for cancer treatment in the immunotherapy era. STATEMENT OF SIGNIFICANCE: Given the benefits of cancer immunotherapy in inducing durable, albeit low rates, of patient response, interest in the immunomodulatory and adjuvant effects of conventional chemotherapy has been re-invigorated. This review article discusses the recent progress towards understanding the synergies between these two treatment types, how they can be used in combination (so-called chemoimmunotherapy), and the potential for drug delivery systems to optimize their effects in translational settings.