A Systemic Complete Response of Metastatic Melanoma to Local Radiation and Immunotherapy

Hiniker, Susan M.; Chen, Daniel S.; Reddy, Sunil; Chang, Daniel T.; Jones, Jennifer C.; Mollick, Joseph A.; Swetter, Susan M.; Knox, Susan J.

doi:10.1593/tlo.12280

Cited by 214 publications

(143 citation statements)

References 13 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…48 The power of such an approach is reproducibly demonstrated in several clinical studies on patients with metastatic melanoma, non-small-cell lung cancer (NSCLC) and brain metastases. 49–51 It is also possible to induce antitumor responses in the tolerogenic microenvironment in liver, as combining ipilimumab with SBRT to a liver lesion is reported to result in durable disease suppression in a patient with metastatic non-small cell lung cancer. 50 These human studies not only demonstrate the safety in combination of SBRT with immunotherapy, but also point out the potential for treating liver malignancy with such an approach.…”

Section: Discussionmentioning

confidence: 99%

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

Tsai

Lee

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Tsai

Lee

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

show abstract

“…The RT was done both for palliation and for synergism with ipilimumab, as it could theoretically render the tumor more immunogenic. 14,15 She rapidly achieved a clinical response to vemurafenib (along with a pruritic rash requiring a dose reduction and a brief course of steroids). The patient developed fevers, chills and marked synovitis in a symmetric fashion, particularly in her wrists, hands and feet.…”

Section: Patientmentioning

confidence: 99%

Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy

Wyluda

Cheng

Schell

et al. 2015

Cancer Biology & Therapy

View full text Add to dashboard Cite

Drabick (2015) Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy, Cancer Biology & Therapy, 16:5, 662-670, DOI: 10.1080/15384047.2015 We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on synergy between conventional or targeted cytotoxic therapy and immunotherapy in cancer treatment.

show abstract

“…4,46 Hiniker et al 47 hypothesized that radiationinduced apoptosis may stimulate an antitumor immune response 48 in the setting of anti-CTLA-4 treatment. They employed radiotherapy combined with immunotherapy as a noninvasive in vivo tumor vaccine strategy in a patient with metastatic melanoma involving the liver.…”

Section: Discussionmentioning

confidence: 99%

An Uncommon Presentation for Cardiac Melanoma

Baykalır¹,

Young²,

Slosky³

et al. 2014

Journal of Patient-Centered Research and Reviews

View full text Add to dashboard Cite

Journal of Patient-Centered Research and Reviews ( JPCRR) is a peerreviewed scientific journal whose mission is to communicate clinical and bench research findings, with the goal of improving the quality of human health, the care of the individual patient, and the care of populations. Recommended Citation An Uncommon Presentation for Cardiac Melanoma AbstractA 66-year-old man with locally advanced malignant melanoma, which was surgically resected, presented with a 3-week history of dizziness, recurrent near-syncopal episodes and generalized weakness. He was found to have sustained polymorphic ventricular tachycardia in the setting of cardiac melanoma. We draw attention to an unusual presentation of malignant melanoma with cardiac metastasis and discuss both its etiology and treatment options. (J Patient-Centered Res Rev. 2014;1:128-132.)

show abstract

A Systemic Complete Response of Metastatic Melanoma to Local Radiation and Immunotherapy

Abstract: The use of radiotherapy in combination with targeted immunotherapy as a noninvasive in vivo tumor vaccine strategy appears to be a promising method of enhancing the induction of systemic immune responses and anti-tumor effect.

Cited by 214 publications

References 13 publications

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

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

Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy

An Uncommon Presentation for Cardiac Melanoma

Contact Info

Product

Resources

About