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Expression of programmed cell death-ligand 1 (PD-L1) is being used as predictive biomarker for immunotherapy in head and neck squamous cell carcinoma (HNSCC). Several antibodies are available for PD-L1 testing and multiple staining and scoring methods are used. This study aimed to compare the performance of two PD-L1 standardized assays (SP263 and 22C3 pharmDx) and one laboratory-developed test (LDT) (22C3) in HNSCC using the tumor proportion score (TPS) and the combined positive score (CPS). Pretreatment biopsies from 147 HNSCC patients were collected in a tissue-microarray (TMA). Serial sections of the TMA were immunohistochemically stained for PD-L1 expression using 22C3 pharmDx on the Dako Link 48 platform, SP263 on the Ventana Benchmark Ultra platform, and 22C3 as an LDT on the Ventana Benchmark Ultra. Stained slides were assessed for TPS and CPS. Cutoffs of ≥1% and ≥50% for TPS and ≥1 and ≥20 for CPS were used. Concordance between the different staining assays was moderate to poor for TPS (intraclass correlation coefficient (ICC) 0.46) as well as for CPS (ICC 0.34). When stratifying patients by clinically relevant cutoffs, considerable differences between the assays were observed: concordance was poor for both TPS and CPS. Generally, SP263 stained a higher percentage of cells than the other assays, especially when using the CPS. Moderate concordance was shown between three different PD-L1 immunohistochemical assays and considerable differences in PD-L1 positivity were observed when using clinically relevant cutoffs. This should be taken into account when using PD-L1 expression to guide clinical practice.

Primary rhabdomyosarcoma (RMS) of the adult prostate is a very rare tumor with only 45 cases published to date. The clinical course of RMS of the prostate is very aggressive, and prognosis is very poor. Here we describe two cases of primary RMS of the prostate of adult patients and discuss the differential diagnosis of RMS with other mesenchymal tumors of prostate. The first patient was a 50-year-old man who clinically presented with urinary retention and hematuria, low serum prostate-specific antigen, moderate prostatomegaly, and multiple metastases as shown by computed tomography. Histological examination revealed a diffuse “small round blue cell” proliferation with an intermingled population of larger cells with rhabdomyoblastic differentiation that showed immunoreactivity for desmin and MYF4 (myogenin). Molecular and cytogenetic studies did not reveal recurrent chromosomal translocations associated with RMSs and other sarcomas. The patient underwent doxorubicin (adriamycin) treatment without disease progression during the whole follow-up period of 7 months. The second patient was a 39-year-old man who presented with urinary retention, an increased serum prostate-specific antigen level, extensive prostatomegaly, enlarged abdominal and inguinal lymph nodes, and skeletal metastases. Histological examination revealed a tumoral proliferation with a small round blue aspect and diffuse immunoreactivity for desmin and MYF4 (myogenin). Fluorescence in situ hybridization revealed a FOXO1 translocation, consistent with a diagnosis of alveolar-type RMS. The patient followed a multimodal treatment and died of the disease after its progression.

To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a+ subsets were identified as most likely skin-derived CD11cint Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11chi dermal DCs with variable expression of langerin. Two other CD1a− LN-residing cDC subsets were characterized as CD14−BDCA3hiCD103− and CD14+BDCA3loCD103+, respectively. Whereas the CD1a+ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a− cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.

Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OSCC) challenges the ability of REIMS to detect low amounts of tumor cells. We evaluate REIMS sensitivity to determine the minimal amount of detected tumors cells during oral cavity cancer surgery. A total of 11 OSCC patients were included in this study. The tissue classification based on 185 REIMS ex vivometabolic profiles from five patients was compared to histopathology classification using multivariate analysis and leave-one-patient-out cross-validation. Vapors were analyzed in vivoby REIMS during four glossectomies. Complementary desorption electrospray ionization–mass spectrometry imaging (DESI-MSI) was employed to map tissue heterogeneity on six oral cavity sections to support REIMS findings. REIMS sensitivity was assessed with a new cell-based assay consisting of mixtures of cell lines (tumor, myoblasts, keratinocytes). Our results depict REIMS classified tumor and soft tissues with 96.8% accuracy. In vivoREIMS generated intense mass spectrometric signals. REIMS detected 10% of tumor cells mixed with 90% myoblasts with 83% sensitivity and 82% specificity. DESI-MSI underlined distinct metabolic profiles of nerve features and a metabolic shift phosphatidylethanolamine PE(O-16:1/18:2))/cholesterol sulfate common to both mucosal maturation and OSCC differentiation. In conclusion, the assessment of tissue heterogeneity with DESI-MSI and REIMS sensitivity with cell mixtures characterized sensitive metabolic profiles toward in vivotissue recognition during oral cavity cancer surgeries.

ABSTRACTWhereas TLR9 agonists are recognized as powerful stimulators of antitumor immunity, GM-CSF has had mixed reviews. In previously reported randomized trials we assessed the effects of local immune modulation in early-stage melanoma with CpG-B alone or with GM-CSF. Here we discuss the added value of GM-CSF and show sex-related differences.