An Abscopal Response to Radiation and Ipilimumab in a Patient with Metastatic Non–Small Cell Lung Cancer

Abstract

A posteriori evidence suggests that radiotherapy to a targeted tumor can elicit an immune-mediated abscopal (ab-scopus, away from the target) effect in non-targeted tumors, when combined with an anti-cytotoxic T-lymphocyte antigen-4 monoclonal (CTLA-4) antibody. Concurrent radiotherapy and ipilimumab (a human monoclonal anti-CTLA-4 antibody) induced immune-mediated abscopal effects in poorly immunogenic pre-clinical tumor models and metastatic melanoma patients. However, no such reports exist for patients with metastatic lung adenocarcinoma. We report the first abscopal response in a treatment-refractory lung cancer patient treated with radiotherapy and ipilimumab. A post-treatment increase in tumor-infiltrating cytotoxic lymphocytes, tumor regression, and normalization of tumor markers was observed. One year after treatment with concurrent radiotherapy and ipilimumab the patient is without evidence of disease.

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

“…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. In this context, RT/IL-12 appears to be a very promising treatment protocol to be further tested in early phase clinical trials on patients with advanced HCC.…”

Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells—A Key Role for Heat-Shock Protein 70 and Receptor CD91

“…Although chemotherapy-induced antigen cross-presentation has been studied extensively, there is a paucity of information about ionizing radiation-mediated antigen cross-presentation. The abscopal effect, observed in patients undergoing radiotherapy, has been demonstrated to be immune-mediated and is likely to involve antigen cross-presentation from irradiated tumors (4,5). Further studies in this field would aid better understanding of how radiotherapy could be made more successful.…”

“…Radiotherapy in prostate cancer has been shown to be associated with increased frequencies of tumor antigen-specific T cells (1). The abscopal effect of radiation (tumor regression at a distant site following localized radiation) has been shown to be immune mediated not only in mouse tumor models (2,3) but also in patients with metastatic melanoma and lung adenocarcinoma (4,5). Furthermore, CD8 þ T-cell infiltration in the irradiated tumor tissue serves as a prognostic factor (4-7), indicating that radiation can switch the immunosuppressive tumor milieu to a proimmune environment.…”

A Blueprint to Advance Colorectal Cancer Immunotherapies

“…Radiotherapy, commonly used for neoadjuvant treatment of rectal cancer and locally advanced colorectal cancers, has broad effects on the immune system through the induction of immunogenic cell death (ICD), maturation of dendritic cells (DCs), and improved cross-presentation (24,25). The abscopal effect (when local radiotherapy is associated with regression of metastatic cancer at a distant site) has been seen in the setting of checkpoint blockade (26,27). The rationale for combining radiotherapy with immunotherapy is to induce an in situ vaccine effect, leading to antigenic spread, uptake of antigens, maturation of DCs, and activation of T cells (28).…”