Combinations of Immunotherapy and Radiation in Cancer Therapy

Vatner, Ralph; Cooper, Benjamin; Vanpouille-Box, Claire; Demaria, Sandra; Formenti, Silvia C.

doi:10.3389/fonc.2014.00325

Cited by 222 publications

(195 citation statements)

References 197 publications

(178 reference statements)

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“…There is growing evidence suggesting that RT may be a practical solution in overcoming his hurdle, and may enhance antitumor efficacy of immunotherapy. 32 Our data presented here demonstrate that RT/IL-12 combination therapy is sufficient to reverse the tolerogenic microenvironment of the liver and hepatic tumors to induce strong antitumor responses in an orthotopic HCC tumor model in mice. This is consistent with the observation that RT synergizes with the antitumor effects of IL-12 in various experimental animal models.…”

Section: Discussionmentioning

confidence: 61%

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

Tsai

Lee

et al. 2018

OncoImmunology

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Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of their antigen presentation activity. RT/IL-12 also significantly reduced accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing production of reactive oxygen species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were significantly activated toward the antitumor phenotype, as revealed by increased expression of CD107a and TNF-α. Together, our data showed that RT/IL-12 treatment could reset the intratumoral immunotolerant state and stimulate activation of antitumor cellular immunity that is capable of eliminating large established HCC tumors.

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Section: Discussionmentioning

confidence: 61%

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment

Tsai

Lee

et al. 2018

OncoImmunology

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“…Interestingly, response in distant metastasis is observed when the primary tumor is irradiated (Blanquicett et al 2005). The mechanism underlying this observation is unclear, but it is likely mediated by immunologic reactions (Vatner et al 2014), thereby supporting the idea that the combination of immune checkpoint inhibitors and radiotherapy warrants further investigation.…”

Section: :12mentioning

confidence: 89%

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cunha

Marcello

Rocha-Santos

et al. 2017

Endocrine-Related Cancer

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Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors. We critically review the literature on preclinical and clinical studies of the immune checkpoint inhibitors as a treatment option for thyroid cancer, ovarian carcinoma, pancreatic adenocarcinoma, adrenocortical carcinoma and neuroendocrine tumors. We present the challenges and the opportunities of using immune checkpoint inhibitors against these endocrine malignancies, highlighting the breakthroughs and pitfalls that have recently emerged.

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“…Radiotherapy-induced tumour cell death leads to release of 'danger signals', such as ecto-calreticulin, high mobility group box 1 and damage-associated molecular patterns, which recruit antigen-presenting cells that prime tumour antigen-specific T-cell responses 107 . Therapeutic strategies to overcome the body's inhibitory immunosuppressive networks provide an opportunity to generate T-cell priming in combination with radiotherapy, inducing antitumour responses outside of the radiotherapy field as well as within the target volume (abscopal effect).…”

Section: Box 4 | Immuno-radio-oncologymentioning

confidence: 99%