Abstract
Simple SummaryConventional anti-cancer treatments for metastatic tumors include chemotherapy and radiation. These approaches can result in harmful side-effects and, in the vast majority of cases, are not curative. Recently, novel treatments have been developed in order to stimulate the host immune system to fight cancer. This type of therapeutic approach, called immunotherapy, has gained a lot of attention in recent years due to discoveries that have deciphered the immunosuppressive role of the tumor microenvironment and underpinning molecular signals. To enhance the delivery of therapeutic drugs to the tumor site, nanoparticle-based delivery systems can be used to reduce off-target effects, and to modulate immune cells present in the tumor microenvironment. This novel therapeutic approach can synergize with other immunotherapies such as immune checkpoint blockade inhibitors and adoptive cell therapy, by enhancing the infiltration of activated immune cells to the tumor site, and by limiting local immunosuppression.A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they provide a way to induce strong anti-tumor immune responses, which are able to fight cancer effectively. However, despite showing great efficacy in hematological and some solid tumors, unresponsiveness, development of therapy resistance and the development of serious adverse effects, limit their capacity to impact the vast majority of tumors. Nanoparticle-based delivery systems are versatile vehicles for a wide variety of molecular cargoes and provide an innovative strategy to improve conventional onco-immunotherapies. They can be finely tuned to release their contents in the tumor microenvironment, or to deliver combinations of adjuvants and antigens in the case of nanovaccines. In this review, we summarize the recent advancements in the field of nanobiotechnology, to remodel the tumor microenvironment and to enhance immunotherapies.
Highlights
The tumor microenvironment (TME) is a complex system composed of proliferating tumor cells, infiltrating immune cells, the extracellular matrix (ECM), blood vessels and a variety of associated cells
Investigation of the molecular mechanisms behind the immunosuppressive state in the TME led to the discovery of immune checkpoint inhibitors (ICIs), which changed the paradigm of cancer treatment, giving rise to novel immunotherapeutic options able to induce a strong infiltration of active immune cells in the TME, with consequent control of tumor growth [3]
ICIs currently used in the clinical setting are monoclonal antibodies able to block the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4)
Summary
The tumor microenvironment (TME) is a complex system composed of proliferating tumor cells, infiltrating immune cells, the extracellular matrix (ECM), blood vessels and a variety of associated cells. Investigation of the molecular mechanisms behind the immunosuppressive state in the TME led to the discovery of immune checkpoint inhibitors (ICIs), which changed the paradigm of cancer treatment, giving rise to novel immunotherapeutic options able to induce a strong infiltration of active immune cells in the TME, with consequent control of tumor growth [3]. ICIs are effective for the treatment of high mutational burden, mismatch repairdeficient or high microsatellite instability tumors, where many mutations are present, favoring the generation of anti-tumor immune responses against specific tumor associated neo-antigens [10]. Another type of novel immunotherapeutic treatment is adoptive cellular transfer (ACT).
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