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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Spotlight Article

The immunosuppressive tumor microenvironment: more than just immune checkpoints

Cellular Immuno-Oncology 4.0

Mark Lowdell

In this issue we have review articles covering a wide spectrum of tumor immunotherapy options; embracing T cells and NK cells as immune effectors and dendritic cells as immune potentiators. These approaches include genetic manipulation to add function via chimeric receptors and control inhibition by targeted gene editing. The one thing they have in common is that the clinical outcome will be determined to a greater or lesser degree by the microenvironment in which the effector cells encounter tumor. In this second decade of the 21st century, oncologists have become true believers in the role of the immune response in the treatment and cure of cancer but it wasn’t always so. This sea change in belief has been driven by the substantial successes of the use of monoclonal antibodies which block immunoregulatory signals delivered by tumor cells to the patient’s cytotoxic T cells; so called ‘immune checkpoint inhibitors’, or CPIs. The first of these was an antibody to CTLA-4 and this was followed by others targeting PD-1. These off-the-shelf monoclonal antibody drugs have had significant success in a wide range of solid cancers including melanoma, non-small cell lung cancer, pancreatic cancer and prostate cancer. Many more are still in clinical trials and alternative therapies using the same regulatory axes are in development – anti-PD-L1, anti-CD39 and anti-CD73 to name but three. Despite these successes, it is fair to say that the majority of cancer patients are not cured by any of the current CPIs, even when used in combination. Nonetheless, the intense interest they have generated has raised awareness of the highly immunosuppressive nature of the tumor microenvironment which has led to a greater understanding of the complex interactions within a tumor and is leading to broader immunopotentiation strategies and the development of drugs to target those.

DOI: 10.18609/cgti.2019.045
Citation: Cell & Gene Therapy Insights 2019; 5(3), 405–409
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