Strategies targeting tumor immune and stromal microenvironment and their clinical relevance

The critical role of tumor microenvironment (TME) in tumor initiation and development has been well recognized after more than a century of studies. Numerous therapeutic approaches targeting TME are rapidly developed including those leveraging nanotechnology, which have been further accelerated since the emergence of immune checkpoint blockade therapies in the past decade. While there are many reviews focusing on TME remodeling therapies via drug delivery and engineering strategies in animal models, state-of-the-art evaluation of clinical development states of TME-targeted therapeutics is rarely found. Here, we illustrate opportunities for integrating nano-delivery system for the development of TME-specific therapeutic regimen, followed by a comprehensive summary of the most up to date approved or clinically evaluated therapeutics targeting cellular and extracellular components within tumor immune and stromal microenvironment, including small molecule and monoclonal antibody drugs as well as nanomedicines. In the end, we also discuss challenges and possible solutions for clinical translation of TME-targeted nanomedicines.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This article summarizes the important role of tumor microenvironment (TME) in tumor initiation and development, as well as the therapeutic approaches targeting TME. It is noted that there are many reviews focusing on TME remodeling therapies in animal models, but the up-to-date evaluation of TME-targeted therapeutics in clinical development is lacking. The article provides a detailed illustration of the opportunities for integrating nano-delivery system for the development of TME-specific therapeutic regimen and a comprehensive summary of approved or clinically evaluated therapeutics targeting cellular and extracellular components within tumor immune and stromal microenvironment, including small molecule and monoclonal antibody drugs as well as nanomedicines. The challenges and possible solutions for clinical translation of TME-targeted nanomedicines are also discussed.