Stimulating Innate Immunity to Enhance Radiation Therapy–Induced Tumor Control

Abstract

Novel ligands that target Toll-like receptors and other innate recognition pathways represent a potent strategy for modulating innate immunity to generate anti-tumor immunity. While many of the current clinically successful immunotherapies target adaptive T-cell responses, both pre-clinical and clinical studies suggest that adjuvants have the potential to enhance the scope and efficacy of cancer immunotherapy. Radiation may be a particularly good partner to combine with innate immune therapies, since it is a highly efficient means to kill cancer cells, but may fail to send the appropriate inflammatory signals needed to act as an efficient endogenous vaccine. This may explain why although radiation therapy is a highly used cancer treatment, true abscopal effects – regression of disease outside the field without additional systemic therapy – are extremely rare. This review focuses on efforts to combine innate immune stimuli as adjuvants with radiation, creating a distinct and complementary approach from T cell targeted therapies to enhance anti-tumor immunity.

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

“…This involvement of TLRs in the pathogenesis of autoimmune diseases and cancers has led to the development novel immunotherapies for these diseases [490][491][492][493][494]. Even TLR mediated immune stimulation approach is now being used to enhance radiation therapy to control tumor growth [495]. For example, various TLRs have now also been implicated in the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD), Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) and repair mechanism is brain disorders [496][497][498][499][500].…”

The effects of local irradiation on circulating lymphocytes in dogs receiving fractionated radiotherapy

“…Localized radiation‐induced tumour cell death can initiate an adaptive host immune response against metastatic cancers through abscopal effects, although it is uncommon . Possibly coupling a radiation‐induced primed immune response along with immunotherapy could prove to be an effective combination therapy against cancer progression .…”

A new standard of care for patients with surgically unresectable stage III non–small cell lung cancer

“…Despite documented evidence of this effect, to the best of our knowledge there have been a minimal number of clinical cases seen in practice. Baird et al speculated that although RT may provide for the release of tumor antigens, it does not provide the necessary costimulation of T cells or cytokine release . The combination of immunotherapy with RT may alleviate this problem.…”

“…Baird et al speculated that although RT may provide for the release of tumor antigens, it does not provide the necessary costimulation of T cells or cytokine release. 47 The combination of immunotherapy with RT may alleviate this problem.…”