Search

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment.

To realize the full promise of terahertz polaritonics (waveguide-based terahertz field generation, interaction, and readout) as a viable spectroscopy platform, much stronger terahertz fields are needed to enable nonlinear and even robust linear terahertz measurements. We use a novel geometric approach in which the optical pump is totally internally reflected to increase the distance over which optical rectification occurs. Velocity matching is achieved by tuning the angle of internal reflection. By doing this, we are able to enhance terahertz spectral amplitude by over 10x compared to conventional single-pass terahertz generation. An analysis of the depletion mechanisms reveals that 3-photon absorption and divergence of the pump beam are the primary limiters of further enhancement. This level of enhancement is promising for enabling routine spectroscopic measurements in an integrated fashion and is made more encouraging by the prospect of further enhancement by using longer pump wavelengths., (© 2022. The Author(s).)

Metallic spintronic terahertz (THz) emitters have become well-established for offering ultra-broadband, gapless THz emission in a variety of excitation regimes, in combination with reliable fabrication and excellent scalability. However, so far, their potential for high-average-power excitation to reach strong THz fields at high repetition rates has not been thoroughly investigated. In this article, we explore the power scaling behavior of tri-layer spintronic emitters using an Yb-fiber excitation source, delivering an average power of 18.5 W (7 W incident on the emitter after chopping) at 400 kHz repetition rate, temporally compressed to a pulse duration of 27 fs. We confirm that a reflection geometry with back-side cooling is ideally suited for these emitters in the high-average-power excitation regime. In order to understand limiting mechanisms, we disentangle the effects on THz power generation by average power and pulse energy by varying the repetition rate of the laser. Our results show that the conversion efficiency is predominantly determined by the incident fluence in this high-average-power, high-repetition-rate excitation regime if the emitters are efficiently cooled. Using these findings, we optimize the conversion efficiency and reach highest excitation powers in the back-cooled reflection geometry. Our findings provide guidelines for scaling the power of THz radiation emitted by spintronic emitters to the milliwatt-level by using state-of-the-art femtosecond sources with multi-hundred-Watt average power to reach ultra-broadband, strong-field THz sources with high repetition rate.

We demonstrate a 13.3 MHz repetition rate, broadband THz source with milliwatt- average power, obtained by collinear optical rectification of a high-power Yb-doped thin-disk laser in the organic crystal BNA (N-benzyl-2-methyl-4-nitroaniline). Our source reaches a maximum THz average power of 0.95 mW with an optical-to-THz efficiency of 4×10 -4 and a spectral bandwidth spanning up to 6 THz at -50 dB, driven by 2.4 W average power (after an optical chopper with duty cycle of 10%), 85 fs-pulses. This high average power excitation was possible without damaging the crystal by using a diamond-heatsinked crystal with significantly improved thermal properties. To the best of our knowledge, this result represents the highest THz average power reported so far using the commercially available organic crystal BNA, showing the potential of these crystals for high average power, high repetition rate femtosecond excitation. The combination of high power, high dynamic range, high repetition rate and broadband spectrum makes the demonstrated THz source highly attractive to improve various time-domain spectroscopy applications. Furthermore, we present a first exploration of the thermal behavior of BNA in this excitation regime, showing that thermal effects are the main limitation in average power scaling in these crystals.

Optical rectification in lithium niobate using the tilted-pulse-front geometry is one of the most commonly used techniques for efficient generation of energetic single-cycle THz pulses and the details of this generation scheme are well understood for high pulse energy driving lasers, such as mJ-class, kHz-repetition rate Ti:Sa amplifier systems. However, as modern Yb-based laser systems with ever increasing repetition rate become available, other excitation regimes become relevant. In particular, the use of more moderate pulse energies (in the few µJ to multi-10 µJ regime), available nowadays by laser systems with MHz repetition rates, have never been thoroughly explored. As increasing the repetition rate of THz sources for spectroscopy becomes more relevant in the community, we present a thorough numerical analysis of this regime using a 2+1-D numerical model. Our work allows us to confirm experimental trends observed in this unusual excitation regime and shows that the conversion efficiency is naturally limited by the small pump beam sizes as a consequence of spatial walk-off between the pump and THz beams. Based on our findings, we discuss strategies to overcome the current limitations, which will pave the way for powerful THz sources approaching the watt level with multi-MHz repetition rates.