Immunotherapy using systemic
immune checkpoint inhibitors (ICI) and
chimeric antigen receptor (CAR) T cells has revolutionized
cancer treatment, but it only benefits a subset of patients. Systemic
immunotherapies cause severe autoimmune toxicities and
cytokine storms. Immune-related adverse events (irAEs) plus the immunosuppressive tumor microenvironment (TME) have been linked to the inefficacy of systemic
immunotherapy. Intratumoral
immunotherapy that increases immunotherapeutic agent bioavailability inside
tumors could enhance the efficacy of
immunotherapies and reduce systemic toxicities. In preclinical and clinical studies, intratumoral administration of immunostimulatory agents from small molecules to xenogeneic cells has demonstrated antitumor effects not only on the injected
tumors but also against noninjected lesions. Herein, we review and discuss the results of these approaches in preclinical models and clinical trials to build the landscape of intratumoral immunotherapeutic agents and we describe how they stimulate the body's immune system to trigger antitumor immunity as well as the challenges in clinical practice. Systemic and intratumoral combination
immunotherapy would make the best use of the body's immune system to treat
cancers. Combining
precision medicine and
immunotherapy in
cancer treatment would treat both the mutated targets in
tumors and the weakened body's immune system simultaneously, exerting maximum effects of the medical intervention.