Combination of External Beam Radiotherapy (EBRT) With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients

Abstract

Purpose The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft tissue sarcoma (STS). Methods and Material Seventeen patients with large (>5 cm) high grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5040 cGy of EBRT, split into 28 fractions and delivered 5 days a week, combined with intratumoral injection of 107 DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed. Results The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; nine patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after one year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4+ T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with 111In labeled DCs demonstrated that these antigen presenting cells need at least 48 hr to start migrating from tumor site. Conclusions Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and need further testing in clinical trials design to assess clinical efficacy.

Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift

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“…A particularly exciting development, hailed by the editors of Science as the scientific breakthrough of 2013 (5), is that novel immunotherapeutic strategies show remarkable responses in some patients, especially if combined with common cytotoxic agents. Radiotherapy and chemotherapeutic agents have been shown to substantially enhance tumorspecific immune responses in well-established tumors (4,(6)(7)(8)(9)(10)(11). The synergy between radiotherapy and immunotherapy stems from radiation-induced effects including (i) immunogenic cell death that locally exposes a wealth of tumor antigens and…”