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Abstract Background Recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) generally has a poor prognosis for patients with limited treatment options. While incorporating immune checkpoint inhibitors (ICIs) has now become the standard of care, the efficacy is variable, with only a subset of patients responding. The complexity of the tumor microenvironment (TME) and the role of tertiary lymphoid structures (TLS) have emerged as critical determinants for immunotherapeutic response. Methods In this study, we analyzed two independently collected R/M HNSCC patient tissue cohorts to better understand the role of TLS in response to ICIs. Utilizing a multi-omics approach, we first performed targeted proteomic profiling using the Nanostring GeoMx Digital Spatial Profiler to quantify immune-related protein expression with spatial resolution. This was further characterized by spatially resolved whole transcriptome profiling of TLSs and germinal centers (GCs). Deeper single-cell resolved proteomic profiling of the TLSs was performed using the Akoya Biosciences Phenocycler Fusion platform. Results Our proteomic analysis revealed the presence of T lymphocyte markers, including CD3, CD45, and CD8, expressing cells and upregulation of immune checkpoint marker PD-L1 within tumor compartments of patients responsive to ICIs, indicative of ‘hot tumor’ phenotypes. We also observed the presence of antigen-presenting cells marked by expression of CD40, CD68, CD11c, and CD163 with upregulation of antigen-presentation marker HLA-DR, in patients responding to ICIs. Transcriptome analysis of TLS and GCs uncovered a marked elevation in the expression of genes related to immune modulation, diverse immune cell recruitment, and a potent interferon response within the TLS structure. Notably, the distribution of TLS-tumor distance was found to be significantly different across response groups (H = 9.28, p = 0.026). The proximity of TLSs to tumor cells was found to be a critical indicator of ICI response, implying that patients with TLSs located further from tumor cells have worse outcomes. Conclusion The study underscores the multifaceted role of TLSs in modulating the immunogenic landscape of the TME in R/M HNSCC, likely influencing the efficacy of ICIs. Spatially resolved multi-omics approaches offer valuable insights into potential biomarkers for ICI response and highlight the importance of profiling the TME complexity when developing therapeutic strategies and patient stratification.

Purpose: The Finke Desert Race is an offroad motorbike and buggy race held annually in central Australia. Owing to the treacherous conditions, this race sees a significant influx of trauma presentations to Alice Springs Hospital, the closest rural hospital. Completion of a tertiary trauma survey (TTS) within 24 hours of a patient's admission is part of standard trauma management. Method: A retrospective analysis was undertaken of trauma presentations managed by general surgery over a 5-day period of the Finke Desert Race weekend, compared to a 3-month control period from February to April of the same year. To be included, patients met the criteria for completion of a TTS. Results: The total number of trauma presentations over the 5-day period of the race weekend was 18 (an incidence rate of 3.6 cases/day), compared to a total of 31 in the 3-month control period (an incidence rate of 0.36 cases/day). The daily rate of major trauma presentations during the Finke race weekend was 9.9 times greater than during the control period. Completion of TTS was missed in only 5.6 % of patients over the Finke weekend, compared to 14.3 % of patients in the control period. The median time from presentation to the emergency department to completion of TTS during the Finke weekend was 20 h 19 min, compared to 20 h 36 min during the control period. Conclusion: Despite the substantial influx of trauma during the race weekend, fewer patients missed having a TTS completed compared to the control period. The median time taken to completion of TTS was similar between the two time periods. These findings suggest that the general surgery department was able to maintain standard trauma management principles.