Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report

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 þ /CD8 þ 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 CD56 bright subset of NK cells, as well as an increase of effector/memory and effector CD8 þ and CD4 þ T cells in the blood while the percentage of CD25 þ FOXP3 þ 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.

Bessere Abwehr durch Thermotherapie jenseits natürlicher Quellen?

“…In der sehr detailreichen Publikation der Kasuistik einer 15-jährigen Patientin mit alveolärem Rhabdomyosarkom konnte durch engmaschige Messungen eine ausgeprägte immunologisch grundsätzlich günstige systemische Wirkung nachgewiesen werden, die die Autoren auf die 22-malige lokoregionäre Kurzwellenhyperthermie parallel zur Radiochemotherapie zurückführten (u. a. erhöhte periphere Konzentrationen bestimmter NK- und T-Zellen, CD56-positiveUntergruppe der NK-Zellen sowie Effektor-/Gedächtnis- und Effektor-CD8þ- und CD4þ-T-Zellen) 13 .…”

“…Diese verbesserte also bei postoperativ rezidiviertem Magenkrebs neben der Tumorprognose auch die Immunfunktionen. Die primäre und sehr rasche Erwärmung des intraabdominell anzutreffenden großen Anteils des Lymphsystems könnte für diesen Effekt verantwortlich sein.In der sehr detailreichen Publikation der Kasuistik einer 15-jährigen Patientin mit alveolärem Rhabdomyosarkom konnte durch engmaschige Messungen eine ausgeprägte immunologisch grundsätzlich günstige systemische Wirkung nachgewiesen werden, die die Autoren auf die 22-malige lokoregionäre Kurzwellenhyperthermie parallel zur Radiochemotherapie zurückführten (u. a. erhöhte periphere Konzentrationen bestimmter NK-und T-Zellen, CD56-positive-Untergruppe der NK-Zellen sowie Effektor-/ Gedächtnis-und Effektor-CD8þ-und CD4þ-T-Zellen)[13].…”

Harnessing Immunotherapy to Enhance the Systemic Anti-Tumor Effects of Thermosensitive Liposomes

“…In fact, very few in vivo studies have evaluated the potential abscopal effects that may be induced by treatment with localized mild hyperthermia alone. Mild hyperthermia is most commonly applied in combination with chemotherapy or radiotherapy treatment, thereby making it difficult to determine any effect of mild hyperthermia alone [62,63]. It was only recently that mild hyperthermia was combined with ICI to enhance abscopal effects [28,64].…”

Chimeric antigen receptor‑natural killer cells: novel insight into immunotherapy for solid tumors (Review)

“…Therefore, silencing NK cell inhibitory receptors and ligands may be conducive to improving the efficiency of CAR-NK cells (56). Furthermore, chemotherapy may also be combined with CAR-NK cells in the treatment of tumors, as chemotherapy can not only eliminate resident cell groups but also induce genotoxic stress and enhance the sensitivity of tumor cells to NK cells (57,58). Furthermore, the safety and clinical effect of the treatment of stage Ⅲ/Ⅳ pancreatic cancer with the combination of percutaneous irreversible electroporation and allogeneic NK cells was demonstrated.…”