The “Trojan Horse” Approach to Tumor Immunotherapy: Targeting the Tumor Microenvironment

Abstract

Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumors may be more effective, particularly those that overcome natural suppressive factors in the tumor microenvironment. The “Trojan Horse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironmental changes within the tumour at the same time as avoiding the systemic toxicity that is often associated with more “full frontal” treatments such as transfer of large numbers of laboratory-expanded tumor-specific cytotoxic T lymphocytes or large intravenous doses of cytokine. Numerous studies have demonstrated that intratumoural therapy has the capacity to minimizing local suppression, inducing sufficient “dangerous” tumor cell death to cross-prime strong immune responses, and rending tumor blood vessels amenable to immune cell traffic to induce effector cell changes in secondary lymphoid organs. However, the key to its success is the design of a sound rational approach based on evidence. There is compelling preclinical data for local immunotherapy approaches in tumor immunology. This review summarises how immune events within a tumour can be modified by local approaches, how this can affect systemic antitumor immunity such that distal sites are attacked, and what approaches have been proven most successful so far in animals and patients.

Effect of IL-17 in the development of colon cancer in mice

“…It is a comprehensive system composed of tumor cells, endothelial cells, fibroblasts, extracellular matrix, and cells associated with immunity and inflammation (5,6). In this complex system, cytokines and various immune cells interact with each other and cooperate to regulate the occurrence, development and invasion and metastasis of tumor.…”

“…In previous studies the focus was on the tumor itself, whereas increasingly investigations have focused on the tumor microenvironment. The tumor microenvironment is a comprehensive system composed of tumor cells, endothelial cells, fibroblasts, extracellular matrix, and all types of cells associated with immunity and inflammation (5,6). It is the internal environment in which the tumor lies during its occurrence and development (7).…”

Antitumor activity of a novel small molecule TLR7 agonist via immune response induction and tumor microenvironment modulation

“…SZU-101 could activated TLR7 NF-κB signaling in a TLR7-specific system at a low concentration of 1 µM after 6 h of stimulation in vitro (15). The anticancer therapies given directly into tumors may be more effective than given systemically, because local therapies could overcome natural suppressive factors in the tumor microenvironment, and induce systemic antitumor immunity (39). For solid tumors, especially breast cancer, direct intratumoral injection is safe and effective (40).…”

A stroma szerepe a tumorok kialakulásában és progressziójában

“…Ezt a gátlást elő lehet segíteni megfelelő citokinkörnyezet megteremtésével, amit intravénás vagy a még hatásosabb intratumorális injektálással lehet megvalósítani. Az antigén-prezentáció és Tc-sejt-aktiválás elősegítése nekrotikus tumorsejtek hozzáadásával -a megfelelő citokinkörnyezetben -különösen hatékony-nyá teheti az immunrendszer antitumor-aktivitását [51]. Bár a klinikai gyakorlat irányában elindított valamenynyi, a tumor mikrokörnyezetét és a stromát célzó terápi-ás szer és módszer felsorolása meghaladja e tanulmány kereteit, összességében megállapítható, hogy a jövőben a rák kezelésének módszereiben jelentős változásokra lehet számítani.…”