TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma

Tuominen, Sanni; Nissi, Linda; Kukkula, Antti; Routila, Johannes; Huusko, Teemu; Leivo, Ilmo; Minn, Heikki; Irjala, Heikki; Löyttyniemi, Eliisa; Ventelä, Sami; Sundvall, Maria; Grönroos, Tove J.

doi:10.3389/fonc.2023.1298333

Cited by 2 publications

References 67 publications

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Pilot Feasibility Study

Rousseau,

Metz,

Kerdraon

et al. 2024

Clin Nucl Med

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Tumor-associated macrophages are targets of interest in triple-negative breast cancer (TNBC). The translocator protein 18 kDa (TSPO) is a sensitive marker for macrophages and holds potential relevance in TNBC stratification. This pilot prospective study (EITHICS, NCT04320030) aimed to assess the potential of TSPO PET/CT imaging using 18F-DPA-714 in primary TNBC, compared with immunohistochemistry, autoradiography, and TSPO polymorphism. Patients and Methods Thirteen TNBC patients were included. They underwent TSPO genotyping (HAB, MAB, LAB), 18F-FDG PET/CT, and breast MRI. Semiquantitative PET parameters were computed. VOIs were defined on the tumor lesion, healthy breast tissue, and pectoral muscle to obtain SUV, tumor-to-background ratio (TBR), and time-activity curves (TACs). Additionally, immunohistochemistry, 3H-DPA-714, and 3H-PK-11195 autoradiography were conducted. Results The majority of TNBC tumors (11/13, 84%) had a preponderance of M2-polarized macrophages with a median proportion of 82% (range, 44%–94%). 18F-DPA-714 PET/CT clearly identified TNBC tumors with an excellent TBR. Three distinct patterns of 18F-DPA-714 TACs were identified, categorized as “above muscular,” “equal to muscular,” and “below muscular” with reference to the muscular background. For the “above muscular” group (2 HAB and 2 MAB), “equal muscular” group (3 HAB, 3 MAB, and 1 LAB), and “below muscular” group (1 LAB and 1 MAB), tumor TACs showed a 18F-DPA-714 accumulation slope of 1.35, 0.62, and 0.22, respectively, and a median SUVmean of 4.02 (2.09–5.31), 1.66 (0.93–3.07), and 0.61 (0.43–1.02). Conclusions This study successfully demonstrated TNBC tumor targeting by 18F-DPA-714 with an excellent TBR, allowing to stratify 3 patterns of uptake potentially influenced by the TSPO polymorphism status. Further studies in larger populations should be performed to evaluate the prognostic value of this new biomarker.

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Pilot Feasibility Study

Rousseau,

Metz,

Kerdraon

et al. 2024

Clin Nucl Med

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The development of a high-plex spatial proteomic methodology for the characterisation of the head and neck tumour microenvironment

Tan,

Berrell,

Donovan

et al. 2024

Preprint

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Mucosal head and neck squamous cell carcinoma (HNSCC) is a debilitating disease that accounts for an estimated 890,000 new cases per year, making it the seventh most common cancer globally. HNSCC is a heterogenous group of cancers that affect various regions of the head and neck which stem from the epithelial cells in the mucosal lining. Despite advancements in chemotherapy, radiotherapy, surgery and immunotherapy, the prognosis of HNSCC has remained relatively unchanged for more than a decade. There is a need to better understand the tumour microenvironment (TME) using spatially resolved approaches, to gain insights into the TME associated with clinical endpoints such as Disease-Free Survival (DFS) and Overall Survival (OS). Here, we profiled 84 mucosal HNSCC tissue samples using next-generation ultra-high plex spatial protein profiling (580-proteins, Immuno-Oncology Proteome Atlas) and spatial transcriptome mapping (18,000 mRNA, Whole Transcriptome Atlas) from Nanostring Technologies (Bruker). Patient specimens were collected during tumour resection, where patients then went on to receive either chemotherapy and/or radiotherapy. Each patient tissue sample was subdivided into tumour and stromal regions prior to digital spatial profiling. We found that patient survival outcomes (both DFS and OS) were associated with anatomical locations and tumour stage. Notably, there were specific proteomic and transcriptomic features in both the tumour and stromal regions that associated with DFS and OS. Independent validation of key proteomic findings (including CD34 and CD44) was performed using single-cell protein profiling (PhenoCycler-Fusion, Akoya Biosciences). Finally, cell type deconvolution based on transcriptomic signatures revealed cell types associated with patient survival. Taken together, this study provides a systematic workflow for discovery and validation of high-plex protein and transcriptomic profiling in mucosal HNSCC.

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TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma

Cited by 2 publications

References 67 publications

Pilot Feasibility Study

Pilot Feasibility Study

The development of a high-plex spatial proteomic methodology for the characterisation of the head and neck tumour microenvironment

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