Strategies to Target Tumor Immunosuppression

The tumor microenvironment is currently in the spotlight of cancer immunology research as a key factor impacting tumor development and progression. While antigen-specific immune responses play a crucial role in tumor rejection, the tumor hampers these immune responses by creating an immunosuppressive microenvironment. Recently, major progress has been achieved in the field of cancer immunotherapy, and several groundbreaking clinical trials demonstrated the potency of such therapeutic interventions in patients. Yet, the responses greatly vary among individuals. This calls for the rational design of more efficacious cancer immunotherapeutic interventions that take into consideration the “immune signature” of the tumor. Multimodality treatment regimens that aim to enhance intratumoral homing and activation of antigen-specific immune effector cells, while simultaneously targeting tumor immunosuppression, are pivotal for potent antitumor immunity

Effects of multi-scattering on the performance of a single-beam acoustic manipulation device.

The effects of multiple scattering on acoustic manipulation of spherical particles using helicoidal Bessel-beams are discussed. A closed-form analytical solution is developed to calculate the acoustic radiation force resulting from a Bessel-beam on an acoustically reflective sphere, in the presence of an adjacent spherical particle, immersed in an unbounded fluid medium. The solution is based on the standard Fourier decomposition method and the effect of multi-scattering is taken into account using the addition theorem for spherical coordinates. Of particular interest here is the investigation of the effects of multiple scattering on the emergence of negative axial forces. To investigate the effects, the radiation force applied on the target particle resulting from a helicoidal Bessel-beam of different azimuthal indexes (m = 1 to 4), at different conical angles, is computed. Results are presented for soft and rigid spheres of various sizes, separated by a finite distance. Results have shown that the emergence of negative force regions is very sensitive to the level of cross-scattering between the particles. It has also been shown that in multiple scattering media, the negative axial force may occur at much smaller conical angles than previously reported for single particles, and that acoustic manipulation of soft spheres in such media may also become possible

Single-shot measurements of the acoustic field of an electrohydraulic lithotripter using a hydrophone array.

Piezopolymer-based hydrophone arrays consisting of 20 elements were fabricated and tested for use in measuring the acoustic field from a shock-wave lithotripter. The arrays were fabricated from piezopolymer films and were mounted in a housing to allow submersion into water. The motivation was to use the array to determine how the shot-to-shot variability of the spark discharge in an electrohydraulic lithotripter affects the resulting focused acoustic field. It was found that the dominant effect of shot-to-shot variability was to laterally shift the location of the focus by up to 5 mm from the nominal acoustic axis of the lithotripter. The effect was more pronounced when the spark discharge was initiated with higher voltages. The lateral beamwidth of individual, instantaneous shock waves were observed to range from 1.5 mm to 24 mm. Due to the spatial variation of the acoustic field, the average of instantaneous beamwidths were observed to be 1 to 2 mm narrower than beamwidths determined from traditional single-point measurements that average the pressure measured at each location before computing beamwidth

Instantaneous beamwidth measurements of an electrohydraulic lithotripter

Acoustic field measurements of electrohydraulic lithotripters (EHL) aretypically conducted with single-element hydrophones and are subject to spatialaveraging errors because the spark source location varies from shock to shock.Linear hydrophone arrays provide a means of obtaining the instantaneous soundfield of EHLs and a more detailed understanding of EHL sound fields. Here,20-element hydrophone arrays were used to study the variability of theinstantaneous acoustic field of an experimental EHL. Calibrated arrays wereplaced at the geometric focus of an EHL and exposed to as many as 1500 shockwaves using excitations of 14, 17 and 20 kV. Instantaneous data were acquiredfrom all 20 hydrophone elements and then were processed for beamwidth, peakpressure location, and peak pressure. Instantaneous beamwidths were found to besmaller than when using a single-element hydrophone approach and peak pressureswere observed to vary more as the excitation voltage increased. © 2010IEEE

Single-shot measurements of the acoustic field of an electrohydraulic lithotripter using a hydrophone array.

Piezopolymer-based hydrophone arrays consisting of 20 elements were fabricated and tested for use in measuring the acoustic field from a shock-wave lithotripter. The arrays were fabricated from piezopolymer films and were mounted in a housing to allow submersion into water. The motivation was to use the array to determine how the shot-to-shot variability of the spark discharge in an electrohydraulic lithotripter affects the resulting focused acoustic field. It was found that the dominant effect of shot-to-shot variability was to laterally shift the location of the focus by up to 5 mm from the nominal acoustic axis of the lithotripter. The effect was more pronounced when the spark discharge was initiated with higher voltages. The lateral beamwidth of individual, instantaneous shock waves were observed to range from 1.5 mm to 24 mm. Due to the spatial variation of the acoustic field, the average of instantaneous beamwidths were observed to be 1 to 2 mm narrower than beamwidths determined from traditional single-point measurements that average the pressure measured at each location before computing beamwidth