Abstract
Introduction An abscopal effect is a clinical observation whereby a local treatment is associated with regression of metastatic cancer at a site distant from the primary location of treatment. Here, we describe the clinical systemic effect induced by regional hyperthermia combined with low-dose chemotherapy and provide immunologic correlates. Case presentation A 15-year-old patient had been diagnosed with alveolar rhabdomyosarcoma (ARMS). All previous treatment options failed in the patient including haploidentical stem cell transplantation and donor lymphocyte infusion. The patient presented with local and metastatic disease, and upon admission, underwent regional hyperthermia combined with low-dose chemotherapy. Immediately following therapy severe skin reactions were observed. Skin biopsies revealed an intraepithelial lymphocytic infiltration dominated by CD3+/CD8+ T cells with a regular network of dendritic cells. Clinical images compared before and during sequential treatment cycles showed complete metabolic response of the local tumor for more than 10 months of therapy. In addition, metastases completely regressed although they were not direct targets of regional hyperthermia. The systemic effect was associated with enhanced frequency of NK cells and T cells expressing the lectin-like natural-killer group 2 D activating receptor (NKG2D), an increase of the CD56bright subset of NK cells, as well as an increase of effector/memory and effector CD8+ and CD4+ T cells in the blood while the percentage of CD25+FOXP3+ regulatory T cells declined. Conclusions Regional hyperthermia combined with low-dose chemotherapy had the potential to create a systemic effect which was associated with activation of NK cells and T cells.
Highlights
An abscopal effect is a clinical observation whereby a local treatment is associated with regression of metastatic cancer at a site distant from the primary location of treatment
Regional hyperthermia combined with low-dose chemotherapy had the potential to create a systemic effect which was associated with activation of NK cells and T cells
Regional hyperthermia added to chemotherapy has gained increasing attention as a promising treatment for high-risk soft tissue sarcoma [10]
Summary
Alveolar rhabdomyosarcoma (ARMS) with PAX3–FKHR translocation is an aggressive subtype of rhabdomyosarcoma in childhood with dismal prognosis [1]. The FDG PET-CT of August 2011 (Figure 1, Panel D) documented no metabolic activity of the abdominal tumor and no evidence of cervical lymph node involvement and bone lesions. During the 3- to 4-week intervals between the 5th and the 11th treatment cycle of regional hyperthermia combined with low-dose chemotherapy, the patient was fully active, played golf and traveled abroad (ECOG 0). Among patient NK cells, the CD56bright NK cell subsets increased significantly in parallel with local tumor shrinkage and regression of metastases, representing more than half of all NK cells and the frequency remained elevated until the 11th cycle, after which a decline was observed concurrent with disease relapse (Figure 3(B)). The two skin biopsies taken at the time of severe skin reactions after application of regional hyperthermia showed an intraepithelial lymphocytic infiltration dominated by CD3þ/CD8þ T cells with a regular network of dendritic cells (Figure 4). Skin-infiltrating CD56- or granzyme B-positive NK cells were not detected by immunohistochemistry in the skin biopsies (data not shown)
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