Strategies for Targeting Cancer Immunotherapy Through Modulation of the Tumor Microenvironment

Cancer immunotherapeutic strategies have shifted the focus of cancer treatment from eradicating the tumor cell by conventional cytotoxic chemotherapy, to educating the immune system to eliminate tumor, thereby preventing the recurrence of cancer. The understanding of tumor microenvironment and its components which generate an immunosuppressive environment is critical in further developing efficient immunotherapies. In this review, we have classified the current immunotherapies based on their effect in modulating the tumor microenvironment. Additionally, we propose the inclusion of nanotechnology and tissue engineering approaches, which provide unique strategies to enhance the therapeutic efficacy and could lead to developing nano/engineered immunotherapies for improved clinical outcomes. Specifically, we focus on criteria for designing nano/engineered immunotherapies and discuss targeted delivery strategies that can optimize the bioavailability of immunotherapies and, in turn, improve the therapeutic outcomes in the treatment of cancer. Lay Summary Several strategies aimed to exploit the therapeutic benefits of immunotherapy are based on alterations of the complex immunosuppressive tumor microenvironment. Such targeted approaches have also been significantly improved by various design criteria based on the concepts of nanotechnology and tissue engineering. The properties of specific targeting, controlled release, and ability to attain enhanced therapeutic effects with low doses conferred by these approaches have immensely helped to surmount the side effects and off-target issues of existing methods. Incorporation of these design criteria while developing various carrier systems for targeted immunotherapy would certainly enhance their clinical translation potential, eventually augmenting anti-tumor responses. Future Work Modulation of tumor microenvironment with strategies discussed in this review will provide additional opportunities to improve cancer immunotherapy, especially in challenging diseases such as pancreatic and brain tumors. Various design attributes with targeted systems would provide numerous advantages, widening the scope of clinical translation and benefits to cancer patients.