Regulatory T cells (Treg) mediate tolerance towards self-antigens by suppression of innate and adaptive immunity. In cancer patients, tumor-infiltrating FoxP31 Treg suppress local anti-tumor immune responses and are often associated with poor prognosis. Markers that are selectively expressed on tumor-infiltrating Treg may serve as targets for immunotherapy of cancer. Here we show that CD103, an integrin mediating lymphocyte retention in epithelial tissues, is expressed at high levels on tumor-infiltrating FoxP31 Treg in several types of murine cancer. In the CT26 model of colon cancer up to 90% of the intratumoral FoxP31 cells expressed CD103 compared to less than 20% in lymphoid organs. CD1031 Treg suppressed T effector cell activation more strongly than CD103 neg Treg. Expression of CD103 on Treg closely correlated with intratumoral levels of transforming growth factor b (TGF-b) and could be induced in a TGF-b-dependent manner by tumor cell lines. In vivo, gene silencing of TGF-b reduced the frequency of CD1031 Treg, demonstrating that CD103 expression on tumor-infiltrating Treg is driven by intratumoral TGF-b. Functional blockade of CD103 using a monoclonal antibody did however not reduce the number of intratumoral Treg, indicating that CD103 is not involved in homing or retention of FoxP31 cells in the tumor tissue.In conclusion, expression of CD103 is a hallmark of Treg that infiltrate TGF-b-secreting tumors. CD103 thus represents an interesting target for selective depletion of tumor-infiltrating Treg, a strategy that may help to improve anti-cancer therapy.

Our retrospective analysis suggests a pivotal role of (18)F-FDG PET in lesion follow-up due to a lower number of false-positive findings after chemotherapy. MRI showed a higher sensitivity and is indispensable for primary staging, evaluation of brain involvement and biopsy planning. Combined MRI/PET analysis improved sensitivity by decreasing the false-negative rate during primary staging indicating a future role of simultaneous whole-body PET/MRI for primary investigation of paediatric histiocytosis.

Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system and is metastatic or high risk for relapse in nearly 50% of cases. Therefore, exact staging with radiological and nuclear medicine imaging methods is crucial for defining the adequate therapeutic choice. Tumor cells express the norepinephrine transporter, which makes metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, an ideal tumor specific agent for imaging. MIBG imaging has several disadvantages, such as limited spatial resolution, limited sensitivity in small lesions and the need for two or even more acquisition sessions. Most of these limitations can be overcome with positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose [FDG]. Furthermore, new tracers, such as fluorodopa or somatostatin receptor agonists, have been tested for imaging neuroblastoma recently. However, MIBG scintigraphy and PET alone are not sufficient for operative or biopsy planning. In this regard, a combination with morphological imaging is indispensable. This article will discuss strategies for primary and follow-up diagnosis in neuroblastoma using different nuclear medicine and radiological imaging methods as well as multimodality imaging.

For the detection of single tumour lesions, registered (18)F-FDG PET/MRI proved to be the methodology of choice for adequate tumour staging. In the examination-based evaluation, MRI alone performed better than (18)F-FDG PET and combined/registered imaging during primary diagnosis. At follow-up, however, the examination-based evaluation demonstrated a superiority of (18)F-FDG PET alone.

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